Immune System

Gut Microbiome and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Insights into Disease Mechanisms.

Nikolova, Ralitsa, Donchev, Deyan, Vaseva, Katya et al.·International journal of molecular sciences·2025

This review examines the connection between gut bacteria and ME/CFS, a condition characterized by exhaustion that worsens after activity. The authors explain how an imbalance in gut bacteria may damage the intestinal barrier, allowing bacterial particles to enter the bloodstream and trigger inflammation throughout the body. They also discuss how changes in gut bacteria might affect the brain, contributing to the brain fog and cognitive problems many ME/CFS patients experience.

Cognitive Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-Aetiology and Potential Treatments.

Bansal, Amolak Singh, Seton, Katharine A, Brooks, Jonathan C W et al.·International journal of molecular sciences·2025

Many ME/CFS patients experience brain fog and difficulty concentrating, which can be as disabling as physical symptoms. This review examined how ongoing low-level inflammation and viral activity in the body may damage thinking and memory by affecting blood flow and nerve function in the brain. The researchers suggest that treating inflammation, controlling viral reactivation, and improving how cells produce energy could potentially help restore cognitive function.

Insights into the Complex Biological Network Underlying Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Dudova, Dobrina, Bozhkova, Martina, Petrov, Steliyan et al.·International journal of molecular sciences·2025

This review brings together research showing that ME/CFS involves multiple body systems going wrong at the same time—including problems with the immune system, energy production in cells, hormone balance, and gut health. These problems appear to feed into each other, creating a cycle that keeps the illness going. The findings suggest ME/CFS is not just one thing breaking down, but rather many interconnected systems all struggling together.

Unravelling the Connection Between Energy Metabolism and Immune Senescence/Exhaustion in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Van Campenhout, Jente, Buntinx, Yanthe, Xiong, Huan-Yu et al.·Biomolecules·2025

This review examines how ME/CFS might involve two connected problems: the body's cells not producing enough energy, and the immune system not working properly. The authors suggest that when cells can't make enough energy, this might directly weaken the immune system, which could explain why patients experience severe fatigue and feel worse after physical activity. The review proposes that treatments targeting both energy production and immune function together might help patients more effectively than treating either problem alone.

The microbiota-gut-brain axis in myalgic encephalomyelitis/chronic fatigue syndrome: a narrative review of an emerging field.

El-Sehrawy, Amr Ali Mohamed Abdelgawwad, Ayoub, Ibtihal Ibrahim, Uthirapathy, Subasini et al.·European journal of translational myology·2025

This review examines how bacteria in your gut may be connected to ME/CFS symptoms like fatigue and brain fog. Researchers looked at studies from 1995 to 2025 about how gut bacteria communicate with the brain and immune system. The review suggests that fixing imbalances in gut bacteria might help treat ME/CFS, though more research is needed to confirm this.

From tradition to healing: the promise of acupuncture in managing chronic fatigue syndrome.

Wang, Delong, Yang, Tiansong, Cui, Yang et al.·Frontiers in medicine·2025

This article reviews what we know about ME/CFS and explores how acupuncture—a traditional Chinese medicine practice—might help treat it. The authors summarize research on what causes ME/CFS, how doctors diagnose it, and discuss both historical and modern approaches to using acupuncture and related techniques to manage symptoms.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: the biology of a neglected disease.

Arron, Hayley E, Marsh, Benjamin D, Kell, Douglas B et al.·Frontiers in immunology·2024

This review examines what we know about ME/CFS by looking at how the disease develops from a combination of genetic factors, infections, and immune problems. The researchers found that ME/CFS appears to result from multiple body systems going wrong at the same time—including the immune system, inflammation, digestive health, and energy production. The study argues that doctors and scientists need to stop looking at ME/CFS as a single problem and instead understand it as a complex condition involving many interconnected issues.

Chronic Fatigue Syndrome: Diagnosis, Treatment, and Future Direction.

Graves, B Sue, Patel, Mitsu, Newgent, Hailey et al.·Cureus·2024

ME/CFS is a serious illness that causes extreme tiredness that doesn't improve with rest and often gets worse with activity. People with ME/CFS also struggle with brain fog, pain, sleep problems, and immune system issues. Right now, doctors don't have a simple blood test or scan to diagnose ME/CFS, which makes it hard to identify and treat the condition properly.

Advancing Research and Treatment: An Overview of Clinical Trials in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Future Perspectives.

Seton, Katharine A, Espejo-Oltra, José A, Giménez-Orenga, Karen et al.·Journal of clinical medicine·2024

This review examined research studies testing various treatments for ME/CFS, including medications and supplements that target different aspects of the illness like immune function, metabolism, and gut health. The authors found that current treatments mainly manage symptoms rather than address the root causes, with very few patients recovering fully. They emphasize that better-designed clinical trials are urgently needed to find treatments that actually work and can be used in real-world medical practice.

Microglia and Sleep Disorders.

Picard, Katherine, Dolhan, Kira, Watters, Jyoti J et al.·Advances in neurobiology·2024

This review examines how microglia—immune cells in the brain and spinal cord—affect sleep and sleep disorders. The authors discuss how sleep problems and lack of sleep can harm brain health and potentially lead to diseases like Alzheimer's and Parkinson's. They specifically look at how microglia may be involved in ME/CFS and other sleep disorders, and what happens to these immune cells when people don't get enough sleep.

Research progress on pathogenesis of chronic fatigue syndrome and treatment of traditional Chinese and Western medicine.

Liu, Tingting, Sun, Weibo, Guo, Shuhao et al.·Autonomic neuroscience : basic & clinical·2024

This review examines what scientists currently understand about ME/CFS—a debilitating condition characterized by extreme fatigue that doesn't improve with rest, along with other symptoms like muscle pain, sore throat, and sleep problems. The authors looked at research on possible causes (like viral infections, stress, and immune system problems) and discussed how both conventional medicine and Traditional Chinese Medicine approaches might help treat the condition.

Autoimmunity's enigmatic role: exploring the connection with myalgic encephalomyelitis/chronic fatigue syndrome.

Batham, Jacob, Dwyer, Jessica, Eaton-Fitch, Natalie et al.·BMC immunology·2024

Researchers reviewed 10 studies to understand whether ME/CFS is caused by autoimmunity—a condition where the immune system attacks the body's own cells. While some signs of autoimmune activity were found in ME/CFS patients, the evidence is mixed and not strong enough to confirm that autoimmunity is the main cause. The authors conclude that ME/CFS is more complex than a straightforward autoimmune disease.

Meta-analysis of natural killer cell cytotoxicity in myalgic encephalomyelitis/chronic fatigue syndrome.

Baraniuk, James N, Eaton-Fitch, Natalie, Marshall-Gradisnik, Sonya·Frontiers in immunology·2024

Researchers combined results from 28 previous studies to confirm that people with ME/CFS have natural killer (NK) cells—a type of immune cell that fights infections and abnormal cells—that work at about half the strength of healthy people's NK cells. This is one of the most reliable biological differences found in ME/CFS. The analysis confirms this is a real, consistent problem in the condition.

Surveying the Metabolic and Dysfunctional Profiles of T Cells and NK Cells in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Maya, Jessica·International journal of molecular sciences·2023

This review examined research on how immune cells (T cells and NK cells) work differently in ME/CFS patients compared to healthy people. The authors found evidence that these immune cells may be exhausted or damaged, similar to what happens in chronic viral infections. Understanding why these immune cells aren't functioning properly could help explain ME/CFS symptoms and guide development of better treatments.

Biomarkers for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a systematic review.

Maksoud, Rebekah, Magawa, Chandi, Eaton-Fitch, Natalie et al.·BMC medicine·2023

Researchers reviewed 101 studies looking for biological markers (biomarkers) that could help diagnose ME/CFS. A biomarker is something measurable in your blood or body that shows a disease is present. While scientists found many potential biomarkers affecting the immune system, energy production, circulation, and other body functions, none have been proven reliable enough to use as a diagnostic test yet.

Therapeutic Implications of the Microbial Hypothesis of Mental Illness.

Savitz, Jonathan, Yolken, Robert H·Current topics in behavioral neurosciences·2023

This review examines whether certain germs—especially viruses like EBV and CMV, and parasites—might contribute to mental illness and ME/CFS. Researchers looked at studies testing whether anti-viral and anti-parasite medications could help treat these conditions, and also explored whether changes in gut bacteria might play a role. The authors found some evidence supporting these connections, though much more research is needed to understand how they work.

Evaluation of viral infection as an etiology of ME/CFS: a systematic review and meta-analysis.

Hwang, Jae-Hyun, Lee, Jin-Seok, Oh, Hyeon-Muk et al.·Journal of translational medicine·2023

Researchers analyzed 64 studies involving nearly 5,000 ME/CFS patients to see if viral infections might cause or trigger the illness. They found that certain viruses—particularly Borna disease virus, human herpesvirus-7, parvovirus B19, enterovirus, and Coxsackie B virus—appeared more frequently in ME/CFS patients compared to healthy people and those with other diseases. While these associations are promising leads, finding a virus more often in patients doesn't prove it causes ME/CFS.

Animal Models for Neuroinflammation and Potential Treatment Methods.

Tamura, Yasuhisa, Yamato, Masanori, Kataoka, Yosky·Frontiers in neurology·2022

This review looked at how ME/CFS may be caused by inflammation in the brain and examined animal studies testing anti-inflammatory treatments. Researchers found that brain inflammation is connected to how severe ME/CFS symptoms are, and that certain compounds with anti-inflammatory properties showed promise in reducing these inflammatory responses in animal models. This suggests that anti-inflammatory medicines might help improve symptoms in ME/CFS patients.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): Where will the drugs come from?

Toogood, Peter L, Clauw, Daniel J, Phadke, Sameer et al.·Pharmacological research·2021

ME/CFS is a serious illness causing extreme fatigue that doesn't improve with rest, along with pain, sleep problems, and difficulty thinking clearly. This review looks at what we currently know about ME/CFS, how doctors diagnose it, and what treatments exist today. The authors examined past research to identify promising targets for new medicines that could help treat ME/CFS in the future.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Human Herpesviruses Are Back!

Ariza, Maria Eugenia·Biomolecules·2021

This review examines whether certain viruses, particularly Epstein-Barr virus (EBV), may play a role in ME/CFS. Earlier research on this topic produced mixed results, leading some scientists to think viruses weren't involved. However, newer research methods have found that specific proteins made by EBV could contribute to immune system and nervous system problems in some ME/CFS patients.

A Comprehensive Update of the Current Understanding of Chronic Fatigue Syndrome.

Noor, Nazir, Urits, Ivan, Degueure, Arielle et al.·Anesthesiology and pain medicine·2021

This review summarizes what researchers currently understand about ME/CFS, a complex illness causing severe fatigue and other symptoms. The condition may involve problems with the immune system, stress response, or nervous system, and can be triggered by infections like Epstein-Barr virus, though not always. Diagnosis requires six months of fatigue plus four symptoms like memory problems, sore throat, or post-exertion malaise, and doctors must rule out other conditions first. Treatment options include therapy, medication, and newer approaches like electrical stimulation, though more research is needed to find the best approaches.

Epstein-Barr Virus and the Origin of Myalgic Encephalomyelitis or Chronic Fatigue Syndrome.

Ruiz-Pablos, Manuel, Paiva, Bruno, Montero-Mateo, Rosario et al.·Frontiers in immunology·2021

This review examines whether Epstein-Barr virus (EBV), a common virus that causes mononucleosis, might play a role in causing ME/CFS in some patients. The researchers found that certain people may have genetic traits that make them more vulnerable to EBV, and in these individuals, the virus might hide from the immune system in a way that leads to ME/CFS symptoms. They suggest that antiviral treatments targeting EBV could potentially help some ME/CFS patients.

Back to the Future? Immunoglobulin Therapy for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Brownlie, Helen, Speight, Nigel·Healthcare (Basel, Switzerland)·2021

This review examined past studies on intravenous immunoglobulin (IV IgG), a blood-based treatment, for ME/CFS. The authors found that while results were previously thought to be mixed, a closer look suggests IV IgG may actually help a meaningful group of patients—particularly those with severe ME/CFS who have specific immune system markers. Some patients experienced temporary worsening of symptoms like headaches during treatment, which may actually indicate the treatment was working rather than causing harm.

The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in myalgic encephalomyelitis/chronic fatigue syndrome: A meta-analysis of public DNA methylation and gene expression data.

Malato, João, Sotzny, Franziska, Bauer, Sandra et al.·Heliyon·2021

This study looked at whether people with ME/CFS have lower levels of a protein called ACE2, which the COVID-19 virus uses to enter cells. The researchers analyzed existing genetic data from ME/CFS patients and found that ACE2 levels were indeed reduced in ME/CFS patients compared to healthy people. The authors suggest this may put ME/CFS patients at higher risk for severe COVID-19 and recommend they be prioritized for vaccination.

Associations Between Psychological and Immunological Variables in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A Systematic Review.

Raanes, Emilie F W, Stiles, Tore C·Frontiers in psychiatry·2021

This review looked at 14 studies to understand how the mind and immune system are connected in ME/CFS. Researchers found that psychological factors like sleep quality, how people manage emotions, and how well they interact with others were linked to immune markers called cytokines. While these connections exist, the evidence is still limited and most studies were done at single points in time rather than following patients over years.

New Insights on the Role of TRP Channels in Calcium Signalling and Immunomodulation: Review of Pathways and Implications for Clinical Practice.

Froghi, Saied, Grant, Charlotte R, Tandon, Radhika et al.·Clinical reviews in allergy & immunology·2021

This review examines how calcium moves into cells through special channels called TRP channels, and how this process affects the immune system. The authors explain that TRP channels play important roles in helping immune cells fight infections and respond to threats. They discuss evidence that problems with these calcium channels may be involved in several diseases, including ME/CFS.

Environmental, Neuro-immune, and Neuro-oxidative Stress Interactions in Chronic Fatigue Syndrome.

Bjørklund, Geir, Dadar, Maryam, Pivina, Lyudmila et al.·Molecular neurobiology·2020

This review looked at how ME/CFS develops by examining immune system problems, oxidative stress (cellular damage from harmful molecules), infections, and nutritional issues. Researchers found that people with ME/CFS often have changes in their immune cells and proteins, along with signs of cellular damage that could explain fatigue, pain, and other symptoms. The study suggests that treatments targeting oxidative stress and nutrition might help, though more research is needed.

A systematic review of cytokines in chronic fatigue syndrome/myalgic encephalomyelitis/systemic exertion intolerance disease (CFS/ME/SEID).

Corbitt, Matthew, Eaton-Fitch, Natalie, Staines, Donald et al.·BMC neurology·2019

Researchers reviewed 15 studies that measured immune signaling molecules called cytokines in people with ME/CFS compared to healthy people. Although many studies have looked at cytokines in ME/CFS, the results were too mixed and inconsistent to show that cytokines could be used as a reliable test for the condition or to confirm a clear role in causing the disease.

[Myalgic encephalomyelitis or chronic fatigue syndrome].

Brinth, Louise, Nielsen, Henrik, Varming, Kim et al.·Ugeskrift for laeger·2019

ME/CFS is a serious condition that causes extreme tiredness affecting both mind and body, along with pain, sleep problems, difficulty thinking clearly, and a symptom called post-exertional malaise where activity makes symptoms worse. Research has found changes in patients' cells, hormones, immune systems, and how their bodies process energy, which could lead to better ways to diagnose and treat this condition.

Pathological Mechanisms Underlying Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Missailidis, Daniel, Annesley, Sarah J, Fisher, Paul R·Diagnostics (Basel, Switzerland)·2019

ME/CFS is a complex condition affecting multiple body systems, and researchers are working to understand what causes it. This review shows that evidence points to problems in the immune system, nervous system, muscle function, metabolism, and gut health in ME/CFS patients. Because patients experience different symptoms and may develop the condition in different ways, finding reliable diagnostic tests remains a key challenge that researchers are actively pursuing.

Epigenetic Components of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Uncover Potential Transposable Element Activation.

Almenar-Pérez, Eloy, Ovejero, Tamara, Sánchez-Fito, Teresa et al.·Clinical therapeutics·2019

This study reviewed research on how ME/CFS may involve changes in how genes are regulated, not the genes themselves. The researchers discovered that dormant DNA sequences called transposable elements—which make up almost half of our genome and were previously thought to be 'junk DNA'—might become activated in ME/CFS patients. This activation could trigger the immune system to attack without an actual infection present.

A systematic review of natural killer cells profile and cytotoxic function in myalgic encephalomyelitis/chronic fatigue syndrome.

Eaton-Fitch, Natalie, du Preez, Stanley, Cabanas, Hélène et al.·Systematic reviews·2019

This review examined research on natural killer cells, which are immune cells that help fight infections and abnormal cells in the body. Scientists found that people with ME/CFS consistently have natural killer cells that don't work as well as they should. This discovery was the most reliable and consistent finding across all the studies reviewed, suggesting it could be an important marker for understanding ME/CFS.

Inflammatory proteins are altered in chronic fatigue syndrome-A systematic review and meta-analysis.

Strawbridge, Rebecca, Sartor, Maria-Laura, Scott, Fraser et al.·Neuroscience and biobehavioral reviews·2019

This research review looked at 42 studies measuring inflammatory proteins (substances in the blood linked to inflammation) in people with ME/CFS compared to healthy people. The researchers found that people with ME/CFS had higher levels of five specific inflammatory proteins, but twelve other proteins were similar to healthy controls. This suggests that inflammation may play a role in ME/CFS for some patients, but it's likely not the main problem for everyone with the condition.

The clinical value of cytokines in chronic fatigue syndrome.

Yang, Tiansong, Yang, Yan, Wang, Delong et al.·Journal of translational medicine·2019

This review examined whether immune system signaling molecules called cytokines could help doctors diagnose or treat ME/CFS. While researchers found that cytokines are abnormal in ME/CFS patients' blood and fluid around the brain, the current evidence shows these markers are not reliable enough to use alone for diagnosis. The review suggests that measuring multiple cytokines together might help doctors better understand what's happening in individual patients, but cytokines are not yet proven as effective treatment targets.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Evidence for an autoimmune disease.

Sotzny, Franziska, Blanco, Julià, Capelli, Enrica et al.·Autoimmunity reviews·2018

This review examines evidence that ME/CFS may be caused by the immune system attacking the body (autoimmune disease). Researchers found that people with ME/CFS have unusual immune patterns, including abnormal antibodies and changes in immune cells. Importantly, a treatment that removes certain immune cells (rituximab) helped about half of ME/CFS patients in clinical trials, suggesting an autoimmune mechanism in at least some people.

[Neurologic Abnormalities in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Review].

Komaroff, Anthony L, Takahashi, Ryosuke, Yamamura, Takashi et al.·Brain and nerve = Shinkei kenkyu no shinpo·2018

This review examines objective, measurable evidence that ME/CFS is a real physical illness, not just a psychological condition. Researchers looked at studies showing that ME/CFS involves problems with the brain, immune system, and how the body uses energy. They found that immune activation—where the body's defense system becomes overactive—may be a key driver of ME/CFS symptoms.

Does the microbiome and virome contribute to myalgic encephalomyelitis/chronic fatigue syndrome?

Newberry, Fiona, Hsieh, Shen-Yuan, Wileman, Tom et al.·Clinical science (London, England : 1979)·2018

This review examines whether changes in the bacteria living in our gut and the viruses that affect those bacteria might contribute to ME/CFS. While previous studies have focused mainly on bacterial changes, this paper points out that viruses—especially those that attack bacteria—are equally important to understand. The authors explain that inconsistencies between different microbiome studies make it hard to draw clear conclusions, and call for more standardized research methods.

Metabolic abnormalities in chronic fatigue syndrome/myalgic encephalomyelitis: a mini-review.

Tomas, Cara, Newton, Julia·Biochemical Society transactions·2018

This review examines research showing that people with ME/CFS have problems with how their bodies use energy at a cellular level. Scientists have found several different metabolic abnormalities—issues with immune function, mitochondria (the cell's power plants), muscle acid buildup, and other energy-related problems—that could potentially be used as biomarkers (measurable signs) to diagnose the disease. However, no single test can yet reliably identify ME/CFS.

Chronic fatigue syndrome and the immune system: Where are we now?

Mensah, Fane Kojo Fosu, Bansal, Amolak Singh, Ford, Brian et al.·Neurophysiologie clinique = Clinical neurophysiology·2017

ME/CFS is a complex illness that causes exhaustion, headaches, and thinking problems, and gets worse with activity. Researchers have suspected for years that the immune system plays a role in ME/CFS, but studies have produced confusing and sometimes contradictory results. This review examines what we currently know about immune system changes in ME/CFS and discusses promising new research directions, including the possibility that certain immune-targeting treatments might help patients improve.

Hypothalamic-Pituitary-Adrenal Hypofunction in Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS) as a Consequence of Activated Immune-Inflammatory and Oxidative and Nitrosative Pathways.

Morris, Gerwyn, Anderson, George, Maes, Michael·Molecular neurobiology·2017

This review examines why people with ME/CFS often have low cortisol levels (a stress hormone). The researchers found that the problem likely starts with an overactive immune system producing excessive inflammatory markers, which then damages the body's stress-hormone system. This is important because it suggests the low cortisol is a consequence of the disease, not its cause.

A Role for the Intestinal Microbiota and Virome in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)?

Navaneetharaja, Navena, Griffiths, Verity, Wileman, Tom et al.·Journal of clinical medicine·2016

This review examines whether infections—particularly viruses in the gut—might trigger ME/CFS. The authors suggest that an imbalance in the gut's microbial and viral communities could be a key factor in developing the disease. They propose that understanding these gut infections could help identify better treatments and ways to prevent ME/CFS.

Chronic fatigue syndrome and circulating cytokines: A systematic review.

Blundell, S, Ray, K K, Buckland, M et al.·Brain, behavior, and immunity·2015

Researchers reviewed 38 studies looking at whether immune proteins called cytokines are elevated in people with ME/CFS. They found that one specific cytokine, TGF-β, was consistently higher in people with ME/CFS compared to healthy people in about 63% of studies. However, most other immune proteins measured were normal, and exercise did not change cytokine levels differently between people with ME/CFS and healthy controls.

Altered immune response to exercise in patients with chronic fatigue syndrome/myalgic encephalomyelitis: a systematic literature review.

Nijs, Jo, Nees, Andrea, Paul, Lorna et al.·Exercise immunology review·2014

When people with ME/CFS exercise, their immune system reacts differently than healthy people's immune systems do. This review looked at 23 studies comparing immune responses to exercise in ME/CFS patients versus healthy people. The key finding is that ME/CFS patients show stronger reactions in certain immune markers and more oxidative stress (damage from chemical imbalances), which may be connected to post-exertional malaise—the worsening of symptoms that happens after activity.

Natural killer cells in patients with severe chronic fatigue syndrome.

Brenu, E W, Hardcastle, S L, Atkinson, G M et al.·Auto- immunity highlights·2013

This review examined how natural killer (NK) cells—a type of white blood cell that fights infections and abnormal cells—work differently in ME/CFS patients. The researchers found that people with ME/CFS often have unusual numbers of NK cells or reduced ability to fight infections, which may help explain why patients suffer from persistent symptoms and recurrent infections. Understanding these immune cell problems could eventually lead to better treatments.

The neuropsychiatric and neuropsychological features of chronic fatigue syndrome: revisiting the enigma.

Christley, Yvonne, Duffy, Tim, Everall, Ian Paul et al.·Current psychiatry reports·2013

This review examined how mental health symptoms like depression and cognitive problems (such as memory and concentration difficulties) commonly occur in ME/CFS patients. Researchers found that depression and ME/CFS often happen together but may involve different biological mechanisms in the body, particularly involving inflammation, immune system dysfunction, and stress hormone imbalances. Understanding these connections helps explain why ME/CFS patients struggle with both physical fatigue and mental health challenges.

Biomarkers for chronic fatigue.

Klimas, Nancy G, Broderick, Gordon, Fletcher, Mary Ann·Brain, behavior, and immunity·2012

This review examines blood tests and biological markers that might help diagnose ME/CFS, since current diagnosis relies only on symptoms. The researchers found that multiple body systems—including the immune system, stress hormones, and nervous system—appear to be disrupted in ME/CFS patients. However, no single test yet reliably identifies the condition, suggesting ME/CFS may involve complex changes across several systems rather than one simple cause.

Meta analysis of Chronic Fatigue Syndrome through integration of clinical, gene expression, SNP and proteomic data.

Pihur, Vasyl, Datta, Somnath, Datta, Susmita·Bioinformation·2011

Researchers combined multiple types of biological data from ME/CFS patients and healthy controls to identify genes that may contribute to ME/CFS and its severity. They found 11 genes of potential importance, with one gene called WASF3 standing out as possibly influencing fatigue through a specific cellular pathway in the brain.

Neuroaetiology of chronic fatigue syndrome: an overview.

Sanders, Patricia, Korf, Jakob·The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry·2008

This review examines several competing theories about what causes ME/CFS. The authors found that while viral infections, brain hormone imbalances, immune problems, and psychological factors are all proposed as causes, none has been definitively proven. The authors suggest that ME/CFS may not be one single disease, but rather several different conditions that produce similar symptoms, which could explain why treatments like cognitive behavioral therapy work for some patients but not others.

[Chronic fatigue syndrome: biochemical examination of blood].

Hakariya, Yukiko, Kuratsune, Hirohiko·Nihon rinsho. Japanese journal of clinical medicine·2007

This review examined blood test abnormalities in ME/CFS patients. While standard blood tests often appear normal in CFS patients despite their many symptoms, specialized blood tests have found problems in the systems that control stress, hormones, and immune function. The authors suggest that ME/CFS may result from brain dysfunction caused by immune chemicals called cytokines or antibodies that attack the body's own cells.

[Viral infections in chronic fatigue syndrome].

Sairenji, Takeshi, Nagata, Keiko·Nihon rinsho. Japanese journal of clinical medicine·2007

This review looked at research on whether viruses and other infections might trigger ME/CFS. Most people with ME/CFS report having a flu-like illness before their symptoms started, which led researchers to investigate if infections could cause long-term immune system problems. The authors summarized what scientists have learned about different viruses, bacteria-like organisms, and other microbes that might be involved in ME/CFS development.

Chronic fatigue syndrome: an update focusing on phenomenology and pathophysiology.

Cho, Hyong Jin, Skowera, Anna, Cleare, Anthony et al.·Current opinion in psychiatry·2006

This review examines what ME/CFS is and how it works in the body. The research shows that ME/CFS is a real condition separate from depression or anxiety, though the official way doctors diagnose it may need updating. Scientists have found signs that the nervous system, immune system, and genetics all play a role, but they still don't fully understand how these pieces fit together.

A systematic review and critical evaluation of the immunology of chronic fatigue syndrome.

Lyall, Marc, Peakman, Mark, Wessely, Simon·Journal of psychosomatic research·2003

Researchers reviewed all the studies looking at immune system problems in ME/CFS patients to see what patterns emerged. They found that results were mixed and often contradictory—some studies showed low natural killer cells, while others didn't, especially when looking at higher-quality research. The review suggests that how studies are designed and conducted can affect whether certain immune changes are found.

Chronic fatigue syndrome: reviewing the research findings.

Johnson, S K, DeLuca, J, Natelson, B H·Annals of behavioral medicine : a publication of the Society of Behavioral Medicine·1999

This review article examines what scientists have learned about ME/CFS by looking at many different studies. Researchers found that ME/CFS is complex—it likely involves multiple causes including viral infections, immune system problems, nervous system dysfunction, and possibly psychological factors. The article emphasizes that ME/CFS affects different people in different ways, suggesting that patients may benefit from being grouped by their symptoms and illness history rather than treated as one uniform condition.

Chronic fatigue syndrome: an immunological perspective.

Vollmer-Conna, U, Lloyd, A, Hickie, I et al.·The Australian and New Zealand journal of psychiatry·1998

This review examines whether immune system problems might cause ME/CFS symptoms, particularly in the brain. The researchers found that while immune chemicals called cytokines are likely involved in ME/CFS, the results from studies measuring these chemicals in the blood have been mixed and unclear. They suggest that abnormal cytokine activity happening directly inside the brain—rather than in the bloodstream—may be more important for explaining the neurological symptoms patients experience.

Chronic fatigue syndrome. 1: Etiology and pathogenesis.

Farrar, D J, Locke, S E, Kantrowitz, F G·Behavioral medicine (Washington, D.C.)·1995

ME/CFS is a serious illness that causes extreme tiredness and many other symptoms, but doctors don't yet fully understand what causes it or how to treat it best. This review looks at research about what might be happening in the body—including problems with the immune system and stress hormone regulation—but notes that no single explanation has been proven. Right now, treatment approaches are based on guesses rather than solid evidence, and we need better ways to identify which patients have which type of ME/CFS.

Pathogenic tracks in fatigue syndromes.

Moutschen, M, Triffaux, J M, Demonty, J et al.·Acta clinica Belgica·1994

This review examined research on ME/CFS and related fatigue conditions that develop after viral infections, looking at five main areas: infectious triggers, immune system problems, muscle function, hormonal imbalances, and psychiatric factors. The authors suggest that abnormalities in the body's stress-hormone system (HPA axis) may be a primary cause, leading to chronic immune activation and reactivation of dormant viruses like those in the herpes family, which then cause muscle weakness and fatigue symptoms.

Clinical correlates of infection with human herpesvirus-6.

Krueger, G R, Klueppelberg, U, Hoffmann, A et al.·In vivo (Athens, Greece)·1994

This review examines connections between human herpesvirus-6 (HHV-6), a common virus most people catch as infants, and various illnesses including ME/CFS. The virus usually stays dormant in the body after infection, but in some people it may reactivate and be linked to several health conditions. The authors reviewed existing knowledge about which diseases show signs of active HHV-6 infection.

Studies of herpesvirus infection in chronic fatigue syndrome.

Straus, S E·Ciba Foundation symposium·1993

This review examined whether common viruses in the herpesvirus family (like Epstein-Barr virus and human herpesvirus 6) cause ME/CFS. Researchers found that while some ME/CFS patients have higher levels of antibodies to these viruses and some cases may start after herpesvirus infection, these viruses are likely not the main cause of the illness for most people.

The pathophysiology of chronic fatigue syndrome: confirmations, contradictions, and conjectures.

Manu, P, Lane, T J, Matthews, D A·International journal of psychiatry in medicine·1992

This 1992 review examined 32 published studies on ME/CFS to identify what researchers had consistently found, disagreed about, or only reported once. The review confirmed that ME/CFS primarily affects middle-aged white women and is often accompanied by depression, but found conflicting evidence about whether infections cause the illness and whether immune treatments help.

Review of laboratory findings for patients with chronic fatigue syndrome.

Buchwald, D, Komaroff, A L·Reviews of infectious diseases·1991

This review examined blood test results from many ME/CFS patients and found several patterns in how their immune systems function differently. The most common findings included weaker natural killer cells (which normally help fight infections), unusual antibody levels, and signs of past Epstein-Barr virus infection. These patterns appeared across multiple studies, suggesting they may be important features of the condition.

Serologic and immunologic responses in chronic fatigue syndrome with emphasis on the Epstein-Barr virus.

Jones, J F·Reviews of infectious diseases·1991

This review examined whether ME/CFS is connected to Epstein-Barr virus (EBV), the virus that causes mono. Researchers found that people with ME/CFS had higher levels of antibodies to EBV compared to healthy people, but this doesn't prove the virus causes the disease. They also found that immune cells called natural killer cells—which help fight infections—work differently in ME/CFS patients, though the findings varied between studies.

An overview of chronic fatigue syndrome.

Krupp, L B, Mendelson, W B, Friedman, R·The Journal of clinical psychiatry·1991

This review examined research on ME/CFS to understand whether the illness is caused by psychological factors, immune system problems, or both. Researchers found that ME/CFS patients experience more disabling fatigue than people with other chronic illnesses, and some have immune system abnormalities. However, many ME/CFS patients have no psychiatric illness, suggesting ME/CFS is a real medical condition separate from depression.

COVID-19-associated neurological and psychological manifestations.

Wilson, Jo Ellen, Gurdasani, Deepti, Helbok, Raimund et al.·Nature reviews. Disease primers·2025

Long COVID is a condition that develops after COVID-19 infection and causes ongoing symptoms for at least 3 months. People with Long COVID commonly experience brain fog, memory problems, anxiety, depression, headaches, sleep issues, and severe exhaustion after physical activity. This review explains what we know about what causes these symptoms and why treatment needs to be personalized based on each person's unique symptoms.

The impact of gut microbiome and diet on post-acute sequelae of SARS-CoV-2 infection.

Reyes, Zabrina, Stovall, Mary Catherine, Punyamurthula, Sanjana et al.·Journal of the neurological sciences·2024

This study looked at how gut bacteria and diet might affect people who develop Long COVID (symptoms that continue months after a COVID-19 infection). Researchers reviewed existing studies to see if changes in gut bacteria linked to worse COVID illness could be improved by eating foods rich in fiber and antioxidants, like those in the Mediterranean Diet. The idea is that a healthier gut might help prevent or reduce Long COVID symptoms.

Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments.

Yong, Shin Jie·Infectious diseases (London, England)·2021

This review examines what we know about Long COVID, an illness that affects some people after they recover from COVID-19 infection. The main symptoms are extreme tiredness and breathing difficulties that last for months, along with brain fog, pain, and heart problems. Researchers found that Long COVID may be caused by lasting damage to organs like the lungs and brain, combined with ongoing inflammation in the body.

The Neurological Manifestations of Post-Acute Sequelae of SARS-CoV-2 infection.

Moghimi, Narges, Di Napoli, Mario, Biller, José et al.·Current neurology and neuroscience reports·2021

This review examined what we know about how COVID-19 can affect the nervous system in people who experience long-term symptoms after infection (called PASC or long COVID). The researchers looked at published studies to understand how common these neurological problems are, who is most at risk, why they happen, and how they might be treated. They found that long COVID can range from mild to severely disabling symptoms that last weeks or longer, and that multiple factors—including lingering inflammation, immune system problems, and possible viral effects on the brain—may play a role.

Myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia - overlap, differences, and emerging insights.

Murovska, Modra, Krumina, Angelika, Araja, Diana et al.·Journal of translational medicine·2026

ME/CFS and fibromyalgia are two different but often overlapping illnesses that cause severe fatigue, pain, and other debilitating symptoms. While they share many similarities, ME/CFS has a distinctive feature called post-exertional malaise—where activity makes symptoms dramatically worse for hours or days—while fibromyalgia does not. This review shows that the two conditions have different immune system patterns and may require different treatment approaches.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): diagnosis and management.

Fan, Jin, Jiao, Jiao, Chang, Hai-Qing et al.·Journal of translational medicine·2025

This comprehensive review examines how ME/CFS is diagnosed and treated based on current medical knowledge. The authors found that ME/CFS is caused by problems with the immune system, energy production in cells, and brain inflammation, but there are currently no definitive blood tests to confirm the disease. Treatment options include both medication approaches (targeting immune dysfunction and cell energy) and non-medication strategies like activity pacing and cognitive behavioral therapy, though doctors now recognize that exercise programs can actually harm some patients.

Differential Characteristics and Comparison Between Long-COVID Syndrome and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Ivanovska, Mariya, Homadi, Maysam Salim, Angelova, Gergana et al.·Biomedicines·2025

This review compared Long-COVID (illness after COVID-19) and ME/CFS (chronic fatigue syndrome), which share similar symptoms like extreme tiredness, difficulty thinking clearly, and problems with the nervous system. While both conditions likely involve immune system problems, viral persistence, and blood vessel issues, they appear to have some differences in how they develop. Currently, there is no cure for either condition, though lifestyle management and rehabilitation help some people.

Gulf War Illness, Fibromyalgia, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID Overlap in Common Symptoms and Underlying Biological Mechanisms: Implications for Future Therapeutic Strategies.

Mantle, David, Domingo, Joan Carles, Golomb, Beatrice Alexandra et al.·International journal of molecular sciences·2025

This review examines four conditions—Gulf War Illness, fibromyalgia, ME/CFS, and long COVID—that share similar symptoms like fatigue, pain, and brain fog. Researchers found that these disorders may share common biological problems, particularly with how cells produce energy (mitochondria), manage stress, and control inflammation. The authors suggest that a supplement called CoQ10 might help because it supports cellular energy production and reduces harmful inflammation.

Biomarkers over Time: From Visual Contrast Sensitivity to Transcriptomics in Differentiating Chronic Inflammatory Response Syndrome and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Dooley, Ming·International journal of molecular sciences·2025

This review examines how doctors can better distinguish between two similar-looking illnesses: Chronic Inflammatory Response Syndrome (CIRS) and ME/CFS. The authors trace how testing methods have evolved from simple vision tests to advanced blood tests that read genetic activity. They suggest that some patients diagnosed with ME/CFS may actually have CIRS, which is treatable if properly identified.

Applicability and adaptation of cognitive behavior therapy for long COVID neuropsychiatric symptoms: a review with insights from ME/CFS.

Takamatsu, Naoki, Kuga, Hironori·BMC infectious diseases·2025

This review examined whether cognitive behavior therapy (CBT)—a talking therapy that helps address thought patterns and behaviors—might help patients with long COVID who experience brain fog, fatigue, and mood problems. The authors compared long COVID to ME/CFS, noting they share many features, and found that while CBT may help some patients feel less tired and think more clearly, it works best when tailored to each person's energy limits and combined with other treatments. Importantly, the authors stress that suggesting CBT does not mean these illnesses are 'all in your head'—they have real physical causes.

Endometriosis and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review and Meta-Analysis.

Compton, Sabrina, Alkabalan, Rodolf, Cadet, Judd et al.·Diagnostics (Basel, Switzerland)·2025

This research found that women with endometriosis (a painful condition affecting the uterus) are nearly three times more likely to develop ME/CFS than women without endometriosis. Both conditions involve similar patterns of immune system problems and ongoing inflammation. The study combined results from multiple research papers to show this connection is real and consistent across different groups of patients.

A review of intravenous immunoglobulin in the treatment of neuroimmune conditions, acute COVID-19 infection, and post-acute sequelae of COVID-19 Syndrome.

Morse, Brinkley A, Motovilov, Katherine, Michael Brode, W et al.·Brain, behavior, and immunity·2025

This review examines intravenous immunoglobulin (IVIG), a treatment that works by providing immune-boosting antibodies, for several conditions including ME/CFS and long COVID. The researchers found that IVIG may help reduce symptoms in some patients, though results have been mixed. The treatment can have side effects and is very expensive, which limits how widely it can be used.

Advancing research on regulatory autoantibodies targeting GPCRs: Insights from the 5th international symposium.

Cabral-Marques, Otavio, Schimke, Lena F, Moll, Guido et al.·Autoimmunity reviews·2025

Scientists at an international conference discussed autoantibodies—immune proteins that can attack the body's own cells—that target structures called GPCRs found on many cells. These autoantibodies were once thought to be harmless side effects but are now recognized as active players in diseases including ME/CFS and long COVID. The conference brought together experts to share new ways of detecting these autoantibodies and ideas for using them as diagnostic tools and treatment targets.

Epigenetic reprograming in myalgic encephalomyelitis/chronic fatigue syndrome: A narrative of latent viruses.

Apostolou, Eirini, Rosén, Anders·Journal of internal medicine·2024

This review examines how viruses, particularly Epstein-Barr virus, may cause lasting changes to how our cells work in ME/CFS patients. The authors found that in about 70% of ME/CFS cases, the illness begins after a viral infection, and viruses can hide in the body while triggering long-term problems with energy, thinking, and immune function. Understanding these viral-triggered changes could help explain why different patients experience ME/CFS differently and may lead to better treatments.

Identifying microRNAs Possibly Implicated in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: A Review.

Tsamou, Maria, Kremers, Fabiënne A C, Samaritakis, Keano A et al.·International journal of molecular sciences·2024

This review examined tiny molecules called microRNAs that may play a role in ME/CFS and fibromyalgia. Researchers looked at existing studies to identify which microRNAs appear to be abnormal in these conditions and what role they might play in causing symptoms. They found that certain microRNAs may be involved in immune system problems, energy production difficulties, and increased pain sensitivity—processes that could help explain why people with these diseases experience fatigue, pain, and other symptoms.

Recent Research Trends in Neuroinflammatory and Neurodegenerative Disorders.

Cohen, Jessica, Mathew, Annette, Dourvetakis, Kirk D et al.·Cells·2024

This review examines how inflammation in the brain and nervous system contributes to several chronic diseases, including ME/CFS and Gulf War Illness. The authors discuss how immune cells and inflammatory molecules can damage the brain and cause persistent symptoms. They highlight promising new laboratory techniques using human stem cells to create brain cells for testing potential treatments.

Chronic inflammatory response syndrome: a review of the evidence of clinical efficacy of treatment.

Dooley, Ming, Vukelic, April, Jim, Lysander·Annals of medicine and surgery (2012)·2024

This review looked at studies about treatments for conditions involving long-term inflammation and fatigue, including ME/CFS. The researchers found that most published studies focused on a treatment approach called the Shoemaker Protocol, which was reported to work better than other treatments tested. However, this review only examined existing published articles rather than conducting new research, so the strength of the evidence depends heavily on the quality of those original studies.

Epigenetic changes in patients with post-acute COVID-19 symptoms (PACS) and long-COVID: A systematic review.

Shekhar Patil, Madhura, Richter, Emma, Fanning, Lara et al.·Expert reviews in molecular medicine·2024

This review examined research on how long-COVID changes the way genes are turned on and off in the body—a process called epigenetics. Researchers found that these changes may affect the immune system, nervous system, and how cells use energy. While the findings are interesting and promise better treatments in the future, current research is still limited in size and quality.

Translating insights into therapies for Long Covid.

Antar, Annukka A R, Cox, Andrea L·Science translational medicine·2024

Long Covid causes a variety of symptoms—like exhaustion, weakness, and brain fog—that last long after a COVID-19 infection ends. This review examines what scientists currently understand about what might cause Long Covid and looks at early laboratory studies and clinical trials testing potential treatments. The authors emphasize that more large-scale research is needed to understand why different people experience different symptoms and to develop effective therapies.

Ear abnormalities in chronic fatigue syndrome (CFS), fibromyalgia (FM), Coronavirus-19 infectious disease (COVID) and long-COVID syndrome (PCS), sick-building syndrome (SBS), post-orthostatic tachycardia syndrome (PoTS), and autoimmune/inflammatory syndrome induced by adjuvants (ASIA): A systematic review.

Skare, Thelma L, de Carvalho, Jozélio Freire, de Medeiros, Italo Roberto Torres et al.·Autoimmunity reviews·2024

This review examined hearing and balance problems (including hearing loss, tinnitus, dizziness, and vertigo) reported across multiple conditions including ME/CFS, fibromyalgia, and long COVID. Researchers searched medical literature from 1990 to 2024 and found that while hearing problems are common, balance problems are less frequently reported. The study suggests these symptoms may stem from immune system dysfunction affecting the inner ear.

ME/CFS and Long COVID share similar symptoms and biological abnormalities: road map to the literature

Anthony L. Komaroff, W. Ian Lipkin·Frontiers in Medicine·2023

Harvard and Columbia researchers conducted a comprehensive review of biological abnormalities in ME/CFS and Long COVID. They found striking overlaps in immune dysregulation, autonomic dysfunction, metabolic disruption, and neurological features. The paper maps the literature to guide researchers working across both conditions.

Understanding, diagnosing, and treating Myalgic encephalomyelitis/chronic fatigue syndrome - State of the art: Report of the 2nd international meeting at the Charité Fatigue Center.

Steiner, Sophie, Fehrer, Annick, Hoheisel, Friederike et al.·Autoimmunity reviews·2023

Over 100 international researchers gathered in Berlin in May 2023 to discuss what we currently know about ME/CFS, how to diagnose it, and how to treat it. The conference highlighted that ME/CFS involves problems with the immune system, blood vessel function, and nervous system control, and that some cases may be triggered by viruses reactivating in the body. Despite growing interest due to Long COVID, ME/CFS remains under-researched and needs significantly more funding to find better diagnostic tests and targeted treatments.

Persistent SARS-CoV-2 Infection, EBV, HHV-6 and Other Factors May Contribute to Inflammation and Autoimmunity in Long COVID.

Vojdani, Aristo, Vojdani, Elroy, Saidara, Evan et al.·Viruses·2023

This review examines how long COVID—a condition where symptoms persist months after a coronavirus infection—may develop through similar mechanisms to ME/CFS. The authors suggest that viral persistence, reactivation of old herpes viruses (like Epstein-Barr virus), immune system dysfunction, and gut microbiome changes may all contribute to ongoing inflammation and autoimmune problems. They propose testing for antibodies and other markers to better identify and treat long COVID.

The microbiome in post-acute infection syndrome (PAIS).

Guo, Cheng, Yi, Boyang, Wu, Jianyong et al.·Computational and structural biotechnology journal·2023

This review examined how the bacteria and other microorganisms living in our bodies—particularly in the gut and mouth—may be altered in patients with prolonged illnesses following infections, including ME/CFS and long COVID. The researchers looked at existing studies to understand whether changes in these microbial communities might contribute to why some people develop long-lasting symptoms after being sick. They explored possible explanations for how these microbial changes could trigger or worsen symptoms in post-infection syndromes.

Aetiological Understanding of Fibromyalgia, Irritable Bowel Syndrome, Chronic Fatigue Syndrome and Classificatory Analogues: A Systematic Umbrella Review.

Kleinstäuber, Maria, Schröder, Andreas, Daehler, Sarah et al.·Clinical psychology in Europe·2023

This study reviewed hundreds of scientific articles about ME/CFS, fibromyalgia, and irritable bowel syndrome to understand what researchers think causes these conditions. The researchers found that most studies focus on biological factors like immune system problems, while far fewer examine psychological or social causes. The review suggests that the best understanding comes from looking at multiple factors together—biological, psychological, and social—rather than just one type of cause.

Pathogenic mechanisms of post-acute sequelae of SARS-CoV-2 infection (PASC).

Sherif, Zaki A, Gomez, Christian R, Connors, Thomas J et al.·eLife·2023

This review examines how COVID-19 can lead to Long COVID, a condition where people experience ongoing fatigue, difficulty with exercise, and brain fog that can last months or years. The researchers explored multiple possible explanations for why this happens, including lingering virus in the body, problems with blood clotting, nerve signaling problems, immune system dysfunction, and reactivation of old viruses like Epstein-Barr. Since Long COVID affects different people in different ways, the authors suggest that different patients may need different treatments.

DNA Methylation Changes in Blood Cells of Fibromyalgia and Chronic Fatigue Syndrome Patients.

Przybylowicz, Patrycja Kamila, Sokolowska, Katarzyna Ewa, Rola, Hubert et al.·Journal of pain research·2023

This study looked at chemical changes called 'methylation' in the blood cells of people with fibromyalgia and chronic fatigue syndrome. Researchers combined data from three previous studies and found that while the specific methylation patterns differed slightly between studies, they consistently affected genes involved in body processes that could explain symptoms like pain and exhaustion. This suggests that methylation changes may play a role in how these conditions develop.

Application and development of fecal microbiota transplantation in the treatment of gastrointestinal and metabolic diseases: A review.

Mahmoudi, Hassan, Hossainpour, Hadi·Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association·2023

This review examines how fecal microbiota transplantation (FMT)—transferring healthy bacteria from a donor's stool to a patient's gut—can treat various diseases. While FMT is very effective for serious C. difficile infections, researchers are exploring whether it might help other conditions including chronic fatigue syndrome, inflammatory bowel disease, and irritable bowel syndrome by restoring a healthy balance of gut bacteria.

DNA Methylation Signatures of Functional Somatic Syndromes: Systematic Review.

Fischer, Susanne, Kleinstäuber, Maria, Fiori, Laura M et al.·Psychosomatic medicine·2023

This review looked at research on DNA changes in people with ME/CFS, fibromyalgia, and irritable bowel syndrome. Scientists found that people with these conditions have different patterns of chemical switches on their genes compared to healthy people, particularly in genes that control immune function and stress response. These differences may help explain why people with ME/CFS experience fatigue, pain, and other symptoms.

Fatigue in ANCA-associated vasculitis (AAV) and systemic sclerosis (SSc): similarities with Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). A critical review of the literature.

van Eeden, Charmaine, Osman, Mohammed S, Cohen Tervaert, Jan Willem·Expert review of clinical immunology·2022

This review examined severe, long-lasting fatigue in patients with certain autoimmune diseases and compared it to ME/CFS. The researchers found that fatigue in these autoimmune diseases shares similarities with ME/CFS, including common immune and metabolic problems. Importantly, this fatigue often persists even after the main disease is brought under control, suggesting it may need different treatment approaches than the underlying condition.

Mindfulness Meditation Interventions for Long COVID: Biobehavioral Gene Expression and Neuroimmune Functioning.

Porter, Nicole, Jason, Leonard A·Neuropsychiatric disease and treatment·2022

This review examines whether mindfulness meditation—a practice involving focused attention and relaxation—might help people with Long COVID and ME/CFS. The authors looked at existing research showing that meditation can reduce fatigue and sleep problems, and may help calm inflammation in the body after viral infections. They suggest that meditation could be a helpful tool to manage symptoms and potentially address some of the underlying biological problems in these conditions.

Genetics of COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome: a systematic review.

Tziastoudi, Maria, Cholevas, Christos, Stefanidis, Ioannis et al.·Annals of clinical and translational neurology·2022

This study looked at genetic research on both COVID-19 and ME/CFS to see if they share common genetic factors that might explain why both conditions cause extreme fatigue. Researchers reviewed 71 studies on COVID-19 genetics and 26 studies on ME/CFS genetics, then identified six genes that appear in both conditions. The findings suggest that immune system dysfunction—specifically problems with inflammation and how immune cells communicate—may play a role in both illnesses.

Breast Implant-Associated Immunological Disorders.

Suh, Lily J, Khan, Imran, Kelley-Patteson, Christine et al.·Journal of immunology research·2022

This review examined reports of illness associated with breast implants, which can cause fatigue, joint pain, difficulty concentrating, and other symptoms similar to those in ME/CFS. Researchers found evidence that breast implants may trigger autoimmune problems in some people, and that removing implants improved symptoms in over half of patients studied. The review suggests that bacterial infections around implants, rather than the implant material itself, might be responsible for these problems.

Analysis of post COVID-19 condition and its overlap with myalgic encephalomyelitis/chronic fatigue syndrome.

Sukocheva, Olga A, Maksoud, Rebekah, Beeraka, Narasimha M et al.·Journal of advanced research·2022

This study compared long-term effects of COVID-19 infection (long-COVID) with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) to see how similar they are. Researchers found that many people who develop long-COVID experience the same symptoms as ME/CFS patients, including severe fatigue, brain fog, headaches, and worsening of symptoms after physical activity. The study suggests that COVID-19 may trigger a ME/CFS-like condition in some people through inflammatory processes in the body.

Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms.

Proal, Amy D, VanElzakker, Michael B·Frontiers in microbiology·2021

Some people who recover from COVID-19 infection continue to experience symptoms for months afterward, a condition called Long COVID or PASC. This review examines multiple biological explanations for why this happens, including organ damage, lingering virus in the body, reactivation of dormant viruses, immune system dysfunction, blood clotting problems, and the body's own immune cells attacking healthy tissues. The authors suggest that different patients likely have different underlying causes, which means different treatments may work best for different people.

Complex syndromes of chronic pain, fatigue and cognitive impairment linked to autoimmune dysautonomia and small fiber neuropathy.

Shoenfeld, Yehuda, Ryabkova, Varvara A, Scheibenbogen, Carmen et al.·Clinical immunology (Orlando, Fla.)·2020

This review brings together evidence suggesting that ME/CFS, along with related conditions like POTS and complex regional pain syndrome, may share a common autoimmune root cause. The researchers found that these conditions are linked by similar patterns: the body's immune system produces antibodies that attack certain nerve receptors, and small nerve fibers become damaged. By understanding these shared mechanisms, doctors may eventually be able to better identify which patients would benefit from immune-targeting treatments.

Shared microglial mechanisms underpinning depression and chronic fatigue syndrome and their comorbidities.

Chaves-Filho, Adriano José Maia, Macedo, Danielle S, de Lucena, David Freitas et al.·Behavioural brain research·2019

This review examined how depression and ME/CFS might share common causes in the brain, specifically through immune cells called microglia. Researchers found that when these brain immune cells become overactive, they may trigger both depression and the fatigue characteristic of ME/CFS. The study suggests that reducing this immune activation could potentially help treat both conditions.

Fatigue, Sleep, and Autoimmune and Related Disorders.

Zielinski, Mark R, Systrom, David M, Rose, Noel R·Frontiers in immunology·2019

Severe fatigue is one of the most disabling symptoms reported by people with autoimmune diseases, including ME/CFS. This review examines how inflammation and the brain contribute to fatigue in these conditions. The authors explain that fatigue involves multiple body systems—including energy supply, metabolism, mood, and sleep—all of which can be disrupted by inflammation.

Recognizing the Leaky Gut as a Trans-diagnostic Target for Neuroimmune Disorders Using Clinical Chemistry and Molecular Immunology Assays.

Simeonova, Denitsa, Ivanovska, Mariya, Murdjeva, Mariana et al.·Current topics in medicinal chemistry·2018

This review examines how a condition called 'leaky gut'—where the intestinal barrier becomes too permeable, allowing harmful bacteria to enter the bloodstream—may contribute to ME/CFS and other conditions affecting mood and energy. The authors summarize available blood and stool tests that can help doctors recognize leaky gut in practice. They identify specific markers (like immune responses to bacterial toxins and inflammatory proteins) that could signal intestinal barrier problems.

Antibodies Against GPCR.

Meyer, Carlotto, Heidecke, Harald·Frontiers in bioscience (Landmark edition)·2018

This review examines how the body's own antibodies (immune proteins) can mistakenly attack receptors on cell surfaces called GPCRs, which are involved in many bodily functions. The authors summarize evidence that these misdirected antibodies may play a role in several diseases, including chronic fatigue syndrome (ME/CFS), heart disease, and autoimmune conditions. Understanding these antibodies could help doctors develop better diagnostic tests and treatments.

A systematic review of the association between fatigue and genetic polymorphisms.

Wang, Tengteng, Yin, Jie, Miller, Andrew H et al.·Brain, behavior, and immunity·2017

Researchers reviewed 50 studies to understand whether differences in our genes (called genetic polymorphisms) might make some people more likely to experience severe fatigue. They found that certain genetic variations in immune system and brain chemistry genes were linked to fatigue across different diseases, including ME/CFS. This suggests that our genes may play a role in determining how tired we become.

Gut Microbiota, Bacterial Translocation, and Interactions with Diet: Pathophysiological Links between Major Depressive Disorder and Non-Communicable Medical Comorbidities.

Slyepchenko, Anastasiya, Maes, Michael, Jacka, Felice N et al.·Psychotherapy and psychosomatics·2017

This review examines how changes in gut bacteria and a 'leaky gut' (where bacteria can cross the intestinal barrier) may contribute to depression and related conditions like ME/CFS. The authors found evidence that diet, gut bacteria composition, and immune system activation are interconnected, and that these connections may explain why depression often occurs alongside conditions like irritable bowel syndrome, ME/CFS, obesity, and diabetes.

The inflammatory hypothesis of mood spectrum broadened to fibromyalgia and chronic fatigue syndrome.

Dell'Osso, Liliana, Bazzichi, Laura, Baroni, Stefano et al.·Clinical and experimental rheumatology·2015

This review examined whether ME/CFS, fibromyalgia, and mood disorders like depression might share similar root causes involving inflammation and immune system dysfunction. Researchers looked at scientific papers from 2000-2014 and found striking similarities in how these conditions affect the brain, nervous system, and immune system. The findings suggest these seemingly different conditions may be connected through common biological mechanisms rather than being completely separate diseases.

Algo-dysfunctional syndromes: a critical digest of the recent literature.

Talotta, Rossella, Atzeni, Fabiola, Bazzichi, Laura et al.·Clinical and experimental rheumatology·2015

This review examines three related conditions—ME/CFS, fibromyalgia, and irritable bowel syndrome—that share similar patterns of pain and fatigue. Researchers found that these conditions likely develop from a combination of factors: genetic predisposition, infections, inflammation, stress hormone problems, changes in how the brain processes pain, and damage to small nerves throughout the body. Treatment works best when doctors use multiple approaches together, including both medications and lifestyle changes.

Biological phenotypes underpin the physio-somatic symptoms of somatization, depression, and chronic fatigue syndrome.

Anderson, G, Berk, M, Maes, M·Acta psychiatrica Scandinavica·2014

This review examined research showing that the physical symptoms experienced in ME/CFS, depression, and somatization (medically unexplained symptoms) have real biological causes, not just psychological ones. The authors found that inflammation, immune system activation, and changes in how the body breaks down certain nutrients are linked to symptoms like fatigue, pain, and autonomic problems. Understanding these biological pathways may help explain why these conditions overlap and why symptoms feel so physically real.

Fecal microbiota transplantation: past, present and future.

Aroniadis, Olga C, Brandt, Lawrence J·Current opinion in gastroenterology·2013

This review examines fecal microbiota transplantation (FMT), a treatment that restores healthy gut bacteria by transferring stool from a healthy donor to a patient. While FMT works very well for a specific bacterial infection, researchers are exploring whether it might help with other conditions including gut disorders and diseases affecting other parts of the body, such as chronic fatigue syndrome. The authors emphasize that more research is needed before FMT can be widely used for conditions beyond its proven application.

Overlap between functional GI disorders and other functional syndromes: what are the underlying mechanisms?

Kim, S E, Chang, L·Neurogastroenterology and motility·2012

Many patients with ME/CFS experience overlapping conditions like irritable bowel syndrome, fibromyalgia, and jaw pain. This review looked at what ME/CFS and similar conditions might have in common. The researchers found that these disorders likely share several underlying problems: how the body processes pain, changes in brain activity, possible past infections, immune system problems, and genetic factors that make some people more vulnerable.

An intriguing and hitherto unexplained co-occurrence: Depression and chronic fatigue syndrome are manifestations of shared inflammatory, oxidative and nitrosative (IO&NS) pathways.

Maes, Michael·Progress in neuro-psychopharmacology & biological psychiatry·2011

Depression and ME/CFS often occur together, and this study suggests they share common biological root causes involving inflammation and oxidative stress (damage to cells). While depression and ME/CFS look different clinically, they appear to involve similar underlying problems with the immune system, energy production, and antioxidant defenses. The authors argue these should be considered connected disorders rather than two separate conditions that happen to co-occur.

Chronic pain and fatigue syndromes: overlapping clinical and neuroendocrine features and potential pathogenic mechanisms.

Clauw, D J, Chrousos, G P·Neuroimmunomodulation·1997

This review examines fibromyalgia and chronic fatigue syndrome, two conditions with overlapping symptoms of pain and exhaustion that have been described throughout medical history under different names. The authors propose that both conditions stem from problems in the central nervous system—the brain and spinal cord—particularly in areas that control hormone levels, pain sensing, and automatic body functions. They suggest that immune system changes seen in these conditions are side effects rather than root causes.

The gastrointestinal microbiota in the development of ME/CFS: a critical view and potential perspectives.

Stallmach, Andreas, Quickert, Stefanie, Puta, Christian et al.·Frontiers in immunology·2024

This review examines whether changes in gut bacteria might play a role in ME/CFS, particularly in cases that develop after infections like COVID-19. The authors found that many ME/CFS patients do show differences in their gut bacteria compared to healthy people, and these changes might trigger immune and inflammatory problems. However, the review concludes that current research hasn't proven that gut bacteria changes actually cause ME/CFS—only that they often occur together.

The "Biology-First" Hypothesis: Functional disorders may begin and end with biology-A scoping review.

Enck, P, Mazurak, N·Neurogastroenterology and motility·2018

This study reviewed research showing that infections can trigger long-lasting functional disorders—conditions where the body doesn't work properly but standard tests appear normal. The authors propose that these disorders start from biological changes (like immune dysfunction or altered gut bacteria) caused by the infection, and that psychological factors develop as a result rather than being the root cause. This challenges the common belief that such conditions are mainly psychological or social in nature.

Chronic fatigue syndrome following infections in adolescents.

Katz, Ben Z, Jason, Leonard A·Current opinion in pediatrics·2013

This review examined teenagers who developed chronic fatigue syndrome (ME/CFS) after infections like mononucleosis. About 13% of teens had ME/CFS six months after infection, dropping to 7% at one year and 4% at two years. The good news is that teenagers generally recover better from post-infectious ME/CFS than adults do.

Gulf war illness, post-HPV vaccination syndrome, and Macrophagic Myofasciitis. Similar disabling conditions possibly linked to vaccine-induced autoimmune dysautonomia.

Martinez-Lavin, Manuel, Tejada-Ruiz, Melina·Autoimmunity reviews·2020

This review looked at three conditions that share similar symptoms—Gulf War illness, post-HPV vaccination syndrome, and Macrophagic Myofasciitis—and found they may have a common cause related to vaccines. All three conditions involve chronic fatigue, widespread pain, and cognitive problems. The authors propose that in some susceptible people, vaccines or multiple vaccines given close together might trigger an autoimmune reaction affecting the nervous system that controls heart rate, blood pressure, and other automatic body functions.

Evidence Refuting the Existence of Autoimmune/Autoinflammatory Syndrome Induced by Adjuvants (ASIA).

Ameratunga, Rohan, Gillis, David, Gold, Michael et al.·The journal of allergy and clinical immunology. In practice·2017

This study examined whether a theory called ASIA (a proposed condition blamed on vaccine adjuvants like aluminum) is supported by scientific evidence. Researchers looked at data from people who received allergen immunotherapy, which contains much more aluminum than vaccines, and found they actually had fewer autoimmune diseases, not more. The study concludes that current evidence does not support the idea that aluminum in vaccines causes autoimmune problems.

Fecal microbiota transplantation broadening its application beyond intestinal disorders.

Xu, Meng-Que, Cao, Hai-Long, Wang, Wei-Qiang et al.·World journal of gastroenterology·2015

This review explores how fecal microbiota transplantation (FMT)—transferring healthy gut bacteria from donors to patients—might help treat conditions beyond intestinal diseases, including chronic fatigue syndrome. The authors found that FMT has shown promise in improving insulin sensitivity in metabolic disease and has produced favorable results in case reports of patients with Parkinson's disease, multiple sclerosis, and chronic fatigue syndrome, suggesting that gut bacteria imbalance may contribute to these conditions.

A narrative review on the similarities and dissimilarities between myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and sickness behavior.

Morris, Gerwyn, Anderson, George, Galecki, Piotr et al.·BMC medicine·2013

This study compares ME/CFS with sickness behavior—the tired, achy feeling you get when you have the flu. While ME/CFS and sickness behavior share some symptoms like fatigue and body pain, they are fundamentally different conditions. Sickness behavior is your body's helpful, temporary response to infection that goes away once you recover, whereas ME/CFS is a chronic disease that persists long-term and involves ongoing immune system problems.

Effects of Qiye Shen'an Pian Combined with Glutamate and Vitamin B1 on Fatigue State, Immune Function and Quality of Life in Patients with Chronic Fatigue Syndrome.

Liu, Jun, Liao, Junfeng, Lin, Fan et al.·Alternative therapies in health and medicine·2024

Researchers tested whether a traditional Chinese herbal supplement (Qiye Shen'an Pian) combined with glutathione and vitamin B1 could help ME/CFS patients feel less tired and improve their immune system. Over 8 weeks, patients receiving the herbal supplement along with the standard treatment showed greater improvements in fatigue levels, immune markers, and overall quality of life compared to those receiving only the standard treatment.

[Bamboo-based medicinal moxibustion for chronic fatigue syndrome: a randomized controlled trial].

Xue, Kai-Yang, Quan, Fei, Tang, Jia-Xuan et al.·Zhongguo zhen jiu = Chinese acupuncture & moxibustion·2023

This study tested whether a traditional Chinese medicine treatment called bamboo-based medicinal moxibustion could help people with chronic fatigue syndrome. Sixty-four patients received either this moxibustion treatment or standard acupuncture over two 6-day courses. The moxibustion group showed greater improvements in fatigue and mood symptoms, and had better immune system markers (T lymphocytes) compared to acupuncture.

Achieving symptom relief in patients with myalgic encephalomyelitis by targeting the neuro-immune interface and optimizing disease tolerance.

Rodriguez, Lucie, Pou, Christian, Lakshmikanth, Tadepally et al.·Oxford open immunology·2023

Researchers tested whether gently stimulating nerve endings inside the nose could help ME/CFS patients feel better. After 8 weeks of treatment, patients showed about a 30% improvement in their overall symptoms. Blood tests showed that ME patients have signs of ongoing immune activation, and those who improved had changes in their immune cells and less inflammation.

B-Lymphocyte Depletion in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial.

Fluge, Øystein, Rekeland, Ingrid G, Lien, Katarina et al.·Annals of internal medicine·2019

Researchers tested whether a drug called rituximab, which reduces B cells (a type of immune cell), could help ME/CFS patients. Over 150 patients received either rituximab infusions or placebo over one year. Unexpectedly, the placebo group actually did slightly better than the treatment group, and neither group showed significant improvement in fatigue or function.

[Acupuncture in the treatment of chronic fatigue syndrome based on "interaction of brain and kidney" in TCM: a randomized controlled trial].

Xu, Yu-Xin, Luo, Hua-Song, Sun, Dong et al.·Zhongguo zhen jiu = Chinese acupuncture & moxibustion·2019

This study tested whether acupuncture could help people with ME/CFS feel less tired and sleep better. Sixty-eight patients were divided into two groups: one received acupuncture twice a week for four weeks along with standard care (rest and vitamins), while the other received only standard care. The acupuncture group showed greater improvements in fatigue, overall wellbeing, and sleep quality compared to the control group.

[Clinical research of auricular gold-needle therapy in treatment of chronic fatigue syndrome of qi deficiency constitution].

Xu, Yi-Yan, Liu, Ji-Hong, Ding, Hui et al.·Zhongguo zhen jiu = Chinese acupuncture & moxibustion·2019

This study tested whether auricular gold-needle therapy (inserting gold needles in specific points on the ear) could help patients with chronic fatigue syndrome caused by qi deficiency, a concept from traditional Chinese medicine. Compared to seed pressure therapy and herbal medicine, the gold-needle treatment resulted in better symptom improvement and stronger immune markers after three months of treatment.

Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment.

Roerink, Megan E, Knoop, Hans, Bronkhorst, Ewald M et al.·Journal of translational medicine·2017

Researchers compared immune signaling molecules (cytokines) in the blood of 50 women with ME/CFS to 48 healthy women and found two markers were elevated in the ME/CFS group: IL-12p40 and CSF-1. They also tested whether a drug called anakinra (which blocks inflammation) could help reduce these markers, but found it did not significantly change cytokine levels after 4 weeks of treatment.

Cytokine signature associated with disease severity in chronic fatigue syndrome patients

Jose G. Montoya, Tyson H. Holmes, Jill N. Anderson et al.·Proceedings of the National Academy of Sciences (PNAS)·2017·n=192

Stanford researchers measured 51 cytokines in 192 ME/CFS patients and 392 healthy controls. Seventeen cytokines were significantly elevated in ME/CFS, with TGF-beta most strongly associated with disease severity. More severe patients had higher cytokine levels, suggesting immune activation scales with illness burden.

Intermittent and graded exercise effects on NK cell degranulation markers LAMP-1/LAMP-2 and CD8+CD38+ in chronic fatigue syndrome/myalgic encephalomyelitis.

Broadbent, Suzanne, Coutts, Rosanne·Physiological reports·2017

This study tested whether two types of exercise programs could help improve immune system function in ME/CFS patients. Twenty-four ME/CFS patients were assigned to either graded exercise, intermittent exercise, or usual care, and researchers measured specific immune cells before and after 12 weeks. Both exercise programs increased markers of natural killer cell activity without making symptoms worse, and improved patients' exercise capacity.

[Efficacy of acupoint catgut embedding combined with ginger-partitioned moxibustion on chronic fatigue syndrome of spleen-kidney yang deficiency syndrome and its effects on T lymphocyte subsets and activity of NK cell].

Xia, Depeng, Chen, Peifang, Du, Peixue et al.·Zhongguo zhen jiu = Chinese acupuncture & moxibustion·2017

This study tested whether a traditional Chinese medicine treatment combining acupuncture with catgut embedding and ginger-based moxibustion could help people with chronic fatigue syndrome. The treatment group showed greater improvements in fatigue symptoms and immune system markers compared to people receiving standard acupuncture alone, with 96.7% reporting benefit.

Cytokine Inhibition in Patients With Chronic Fatigue Syndrome: A Randomized Trial.

Roerink, Megan E, Bredie, Sebastian J H, Heijnen, Michael et al.·Annals of internal medicine·2017

Researchers tested whether a drug called anakinra, which reduces inflammation in the body, could help reduce fatigue in women with ME/CFS. Over 4 weeks, patients received either anakinra injections or placebo (dummy injections), and both groups were followed for an additional 20 weeks. The drug did not significantly improve fatigue or other symptoms compared to placebo, though some patients experienced injection site reactions.

Graded versus Intermittent Exercise Effects on Lymphocytes in Chronic Fatigue Syndrome.

Broadbent, Suzanne, Coutts, Rosanne·Medicine and science in sports and exercise·2016

This study tested whether two types of exercise programs—graded (gradually increasing intensity) and intermittent (alternating intense and easy periods)—could help improve immune system function in ME/CFS patients. Over 12 weeks, both exercise types led to increases in certain immune cells and improved fitness without making symptoms worse. Intermittent exercise appeared to work slightly better than graded exercise for boosting immune activation.

Investigating neural mechanisms of change of cognitive behavioural therapy for chronic fatigue syndrome: a randomized controlled trial.

van Der Schaaf, Marieke E, Schmits, Iris C, Roerink, Megan et al.·BMC psychiatry·2015

This study investigated how cognitive behavioral therapy (CBT) works for ME/CFS by examining brain imaging and blood markers before and after treatment. Researchers compared 60 ME/CFS patients receiving CBT with 30 on a waiting list and 30 healthy controls to see how their brains changed and whether hormone and immune markers were involved in recovery.

Randomized clinical trial to evaluate the efficacy and safety of valganciclovir in a subset of patients with chronic fatigue syndrome.

Montoya, Jose G, Kogelnik, Andreas M, Bhangoo, Munveer et al.·Journal of medical virology·2013

This study tested whether a antiviral medication called valganciclovir could help ME/CFS patients who had evidence of past infection with two common viruses (HHV-6 and EBV). Thirty patients received either the medication or placebo for 6 months. Those taking valganciclovir showed improvements in mental fatigue, overall fatigue, and cognitive function within the first 3 months, and these improvements lasted through the end of the study. The medication also produced changes in immune cell counts that suggest the patient's immune system was shifting toward a different state.

Bifidobacterium infantis 35624 modulates host inflammatory processes beyond the gut.

Groeger, David, O'Mahony, Liam, Murphy, Eileen F et al.·Gut microbes·2013

This study tested whether a beneficial gut bacterium called Bifidobacterium infantis 35624 could reduce inflammation in people with ME/CFS, along with people who have other inflammatory conditions like ulcerative colitis and psoriasis. Participants took either the bacterium or placebo for 6-8 weeks, and researchers measured inflammatory markers in their blood. The bacterium reduced multiple inflammatory markers across all three conditions, suggesting that gut bacteria can influence immune system activity throughout the whole body, not just in the gut.

[Impacts on chronic fatigue syndrome of qi deficiency syndrome and T cell subgroups in patients treated with acupuncture at selective time].

Ling, Jia-Yan, Shen, Lin, Liu, Qing et al.·Zhongguo zhen jiu = Chinese acupuncture & moxibustion·2013

This study tested whether acupuncture given at a specific time of day (9-11 AM) could help ME/CFS patients better than acupuncture given at other times. Eighty patients received either timed acupuncture or standard acupuncture over two 10-day treatment sessions. The timed acupuncture group showed greater improvement in fatigue, particularly mental fatigue, and showed better changes in immune cell counts.

Effects of the intelligent-turtle massage on the physical symptoms and immune functions in patients with chronic fatigue syndrome.

Wang, Ji-hong, Chai, Tie-qu, Lin, Guo-hua et al.·Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan·2009

This study tested whether a specialized massage technique called 'intelligent-turtle massage' could help people with ME/CFS. Researchers compared this new technique to standard massage in 182 patients and found that the intelligent-turtle massage was better at reducing symptoms and appeared to strengthen certain immune system markers (IgA, IgM, and IgG). While the results suggest this massage method may offer benefits, it was a relatively small study from 2009.

[Effect of lixu jieyu recipe in treating 75 patients with chronic fatigue syndrome].

Zhang, Zhen-Xian, Wu, Li-Li, Chen, Min·Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine·2009

Researchers tested a traditional Chinese herbal medicine called Lixu Jieyu Recipe (LJR) in 75 ME/CFS patients over 3 months. Compared to patients who received standard vitamins and supplements, those taking LJR reported significantly greater improvements in fatigue and psychological symptoms, and showed better improvements in certain immune cell counts that are often abnormal in ME/CFS.

A placebo-controlled, double-blind, randomized controlled trial of a natural killer cell stimulant (BioBran MGN-3) in chronic fatigue syndrome.

McDermott, C, Richards, S C M, Thomas, P W et al.·QJM : monthly journal of the Association of Physicians·2006

This study tested whether a supplement called BioBran MGN-3 could reduce fatigue in people with ME/CFS by boosting immune cells called natural killer cells. Seventy-one patients took either the supplement or a placebo for 8 weeks. Both groups improved during the study, but the supplement group did not improve significantly more than the placebo group, suggesting the supplement itself was not the reason for improvement.

Treatment with staphylococcus toxoid in fibromyalgia/chronic fatigue syndrome--a randomised controlled trial.

Zachrisson, Olof, Regland, Björn, Jahreskog, Marianne et al.·European journal of pain (London, England)·2002

Researchers tested whether injections of a substance called staphylococcus toxoid could help people with fibromyalgia and chronic fatigue syndrome (ME/CFS). Over 6 months, 100 patients received either the active treatment or placebo injections. Two-thirds of patients receiving the active treatment reported improvement compared to only one-fifth receiving placebo, suggesting the treatment may help some people with these conditions.

Consequences of live poliovirus vaccine administration in chronic fatigue syndrome.

Vedhara, K, Llewelyn, M B, Fox, J D et al.·Journal of neuroimmunology·1997

Researchers gave some ME/CFS patients a live polio vaccine while others received a placebo, and followed them to see what happened. The good news is that the vaccine did not make ME/CFS symptoms worse. However, blood tests showed that ME/CFS patients had some differences in how their immune systems responded to the vaccine compared to healthy people, including differences in fighting off the virus and in certain immune cell counts.

Clinical improvement in chronic fatigue syndrome is not associated with lymphocyte subsets of function or activation.

Peakman, M, Deale, A, Field, R et al.·Clinical immunology and immunopathology·1997

Researchers tested whether immune system changes were linked to ME/CFS symptoms and whether treating ME/CFS would change immune markers. They measured various immune cell types in 43 ME/CFS patients and healthy controls before and after treatment. They found that most immune markers were similar between patients and controls, and improvements in symptoms were not connected to changes in immune cells.

Intravenous immunoglobulin is ineffective in the treatment of patients with chronic fatigue syndrome.

Vollmer-Conna, U, Hickie, I, Hadzi-Pavlovic, D et al.·The American journal of medicine·1997

This study tested whether intravenous immunoglobulin (IVIg)—a blood product containing antibodies—could help treat ME/CFS. Ninety-nine patients received either IVIg at different doses or a placebo monthly for 3 months. The researchers found that IVIg at any dose did not improve symptoms, quality of life, or daily functioning compared to placebo. Side effects were common in both groups, suggesting IVIg is not an effective treatment for ME/CFS.

Lessons from a pilot study of transfer factor in chronic fatigue syndrome.

De Vinci, C, Levine, P H, Pizza, G et al.·Biotherapy (Dordrecht, Netherlands)·1996

This small study tested whether Transfer Factor (TF), a substance derived from immune cells, could help people with ME/CFS feel better. Twenty patients received either TF or a placebo, and researchers tracked their symptoms and blood levels of viruses linked to ME/CFS. Twelve patients showed improvement within 3-6 weeks of starting treatment, though the study was too small to prove TF definitely works.

Double-blind placebo-controlled study of the efficacy of oral terfenadine in the treatment of chronic fatigue syndrome.

Steinberg, P, McNutt, B E, Marshall, P et al.·The Journal of allergy and clinical immunology·1996

Researchers tested whether terfenadine, an antihistamine medication, could help reduce ME/CFS symptoms in 28 patients over two months. Despite finding that most ME/CFS patients had signs of allergies, the medication showed no benefit for fatigue, functioning, or overall well-being compared to placebo. This study suggests antihistamines are unlikely to be an effective treatment for ME/CFS.

alpha-Interferon treatment of patients with chronic fatigue syndrome.

See, D M, Tilles, J G·Immunological investigations·1996

Researchers gave 30 ME/CFS patients either a drug called interferon or a placebo (inactive treatment) in a controlled trial to see if it would help. While the drug boosted a type of immune cell called Natural Killer cells in the blood, it only actually improved symptoms and quality of life for patients who had specifically low NK cell function at the start. For those 7 patients, their symptoms got significantly better after 12 weeks of treatment.

A controlled clinical trial with a specifically configured RNA drug, poly(I).poly(C12U), in chronic fatigue syndrome.

Strayer, D R, Carter, W A, Brodsky, I et al.·Clinical infectious diseases : an official publication of the Infectious Diseases Society of America·1994

This study tested whether an experimental drug called poly(I).poly(C12U) could help people with ME/CFS. Ninety-two patients received either the drug or a placebo for 24 weeks. Those who received the drug showed improvements in daily functioning, mental clarity, ability to exercise, and overall performance compared to those who received placebo.

Changes in the 2-5A synthetase/RNase L antiviral pathway in a controlled clinical trial with poly(I)-poly(C12U) in chronic fatigue syndrome.

Suhadolnik, R J, Reichenbach, N L, Hitzges, P et al.·In vivo (Athens, Greece)·1994

This study looked at whether a drug called poly(I)-poly(C12U) could help ME/CFS by measuring specific immune markers in the blood. Researchers found that people with ME/CFS had higher levels of these immune markers than healthy controls, and when treated with the drug, these markers decreased along with improvements in thinking and memory problems.

Immunological and psychological dysfunction in patients receiving immunotherapy for chronic fatigue syndrome.

Hickie, I, Lloyd, A, Wakefield, D·The Australian and New Zealand journal of psychiatry·1992

This study examined whether depression and immune system problems in ME/CFS patients are connected. Researchers gave 33 patients with ME/CFS either a high-dose immune treatment or placebo and tracked changes in both mood and immune markers. Patients who received the real treatment showed that when their immune systems improved, their depression symptoms also improved together, suggesting these problems may be linked to the same underlying cause rather than one causing the other.

A controlled trial of intravenous immunoglobulin G in chronic fatigue syndrome.

Peterson, P K, Shepard, J, Macres, M et al.·The American journal of medicine·1990

Researchers tested whether a blood product called intravenous immunoglobulin G (IV IgG) could help people with ME/CFS by giving it to 28 patients every month for 6 months. Although some patients had low levels of this protein at the start, IV IgG did not improve fatigue, daily functioning, or overall health compared to placebo, even though the treatment restored protein levels to normal.

A double-blind, placebo-controlled trial of intravenous immunoglobulin therapy in patients with chronic fatigue syndrome.

Lloyd, A, Hickie, I, Wakefield, D et al.·The American journal of medicine·1990

This study tested whether a high-dose immune protein treatment (intravenous immunoglobulin) could help people with ME/CFS. Researchers gave 49 patients either the treatment or placebo and measured changes in fatigue, mood, physical function, and immune markers. More people who received the treatment reported significant improvement and returned to work and activities compared to those who received placebo, suggesting immune system problems may play a role in ME/CFS.

Immune modulation with a staphylococcal preparation in fibromyalgia/chronic fatigue syndrome: relation between antibody levels and clinical improvement.

Zachrisson, O, Colque-Navarro, P, Gottfries, C G et al.·European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology·2004

Researchers tested whether a vaccine made from killed bacteria could help people with ME/CFS and fibromyalgia by stimulating their immune system. Half of 28 patients received the vaccine and half received placebo over 6 months. Patients who received the vaccine developed antibodies (immune proteins) against bacterial toxins, and those with stronger antibody responses showed more clinical improvement.

Lymphocyte markers and natural killer cell activity in fibromyalgia syndrome: effects of low-dose, sublingual use of human interferon-alpha.

Russell, I J, Vipraio, G A, Michalek, J E et al.·Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research·1999

This study examined immune system cells in people with fibromyalgia and compared them to healthy people. Researchers gave some fibromyalgia patients very small doses of interferon-alpha (a substance the body makes to fight infections) under the tongue for 6 weeks, while others received placebo. The study found some changes in certain immune cells, but the results did not show the same type of immune system abnormalities that have been found in chronic fatigue syndrome patients.

Charting the circulating proteome in ME/CFS using cross-system profiling to uncover mechanistic insights.

Hoel, August, Hoel, Fredrik, Dyrstad, Sissel Elisabeth et al.·Cell reports. Medicine·2026

Researchers analyzed thousands of proteins in the blood of ME/CFS patients and compared them to healthy people. They found significant differences in protein patterns, including too much of certain immune-related proteins and too little of proteins normally made by muscles. These differences might help explain why ME/CFS causes such severe exhaustion and could eventually lead to new ways to diagnose or treat the condition.

Multi-omics identifies lipid accumulation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome cell lines: a case-control study.

Missailidis, Daniel, Armstrong, Christopher W, Anderson, Dovile et al.·Journal of translational medicine·2026

Researchers studied immune cells from people with ME/CFS and found that these cells accumulate abnormal amounts of fats (lipids) compared to healthy controls. The cells also show changes in how they process and use these fats for energy. This discovery suggests that problems with how the body handles fats might be part of what makes ME/CFS different at the cellular level.

Development and validation of blood-based diagnostic biomarkers for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) using EpiSwitch® 3-dimensional genomic regulatory immuno-genetic profiling.

Hunter, Ewan, Alshaker, Heba, Bundock, Oliver et al.·Journal of translational medicine·2025

Researchers developed a new blood test called EpiSwitch®CFS that may help diagnose ME/CFS by detecting specific patterns in how DNA is organized in blood cells. When tested on stored blood samples from 47 ME/CFS patients and 61 healthy people, the test correctly identified 92% of ME/CFS patients and correctly ruled out 98% of healthy controls. This could potentially help doctors diagnose ME/CFS more reliably, since there is currently no standard blood test for the condition.

The Clinical Relevance of Mast Cell Activation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Rohrhofer, Johanna, Ebner, Lilian, Schweighardt, Johannes et al.·Diagnostics (Basel, Switzerland)·2025

This study looked at whether mast cells—immune cells that release chemicals causing inflammation—play a role in ME/CFS. Researchers surveyed 687 ME/CFS patients and reviewed records from 383 others, finding that about 25% had signs of problematic mast cell activation. Importantly, patients with mast cell problems who received targeted treatment reported better symptom relief than those without mast cell involvement, suggesting this might be a treatable subtype of ME/CFS.

Deep sequencing of BCR heavy chain repertoires in myalgic encephalomyelitis/chronic fatigue syndrome.

Ryback, Audrey A, Cowan, Graeme J M·Frontiers in immunology·2025

This study examined immune system cells called B cells in people with ME/CFS to see if the disease might be caused by chronic infections or autoimmune problems. Researchers compared blood samples from 25 patients with mild/moderate ME/CFS, 36 with severe ME/CFS, healthy people, and people with multiple sclerosis. They found that ME/CFS patients' B cells did not show the typical patterns expected if chronic infection or autoimmunity were the main cause, though they did notice a difference in the balance of certain antibody types in milder cases.

Mapping the complexity of ME/CFS: Evidence for abnormal energy metabolism, altered immune profile, and vascular dysfunction.

Heng, Benjamin, Gunasegaran, Bavani, Krishnamurthy, Shivani et al.·Cell reports. Medicine·2025

This study examined blood samples from ME/CFS patients and healthy people to understand what goes wrong in the body. Researchers found that immune cells in ME/CFS patients are struggling to make energy (ATP), the fuel that powers our cells. The immune system also showed signs of being immature or worn out, and blood proteins related to clotting and blood vessel problems were elevated, suggesting blood vessel dysfunction may contribute to ME/CFS symptoms.

Cerebrospinal fluid immune phenotyping reveals distinct immunotypes of myalgic encephalomyelitis/chronic fatigue syndrome.

Bastos, Victoria C, Greene, Kerrie A, Tabachnikova, Alexandra et al.·Journal of immunology (Baltimore, Md. : 1950)·2025

Researchers studied cerebrospinal fluid (the fluid around the brain and spinal cord) from people with ME/CFS and found that the immune system appears to work differently in different patients. They discovered two distinct patient groups with different immune patterns and pathogen exposure histories, even though both groups had similar symptoms. This suggests that ME/CFS may not be a single disease, but rather several related conditions with different underlying causes.

Circulating cell-free RNA signatures for the characterization and diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome.

Gardella, Anne E, Eweis-LaBolle, Daniel, Loy, Conor J et al.·Proceedings of the National Academy of Sciences of the United States of America·2025

Researchers analyzed tiny pieces of RNA floating in the blood of people with ME/CFS and compared them to healthy people. They used a computer program to identify a pattern of these RNA pieces that could help diagnose ME/CFS with 77% accuracy. The study found that people with ME/CFS have different levels of immune cells releasing material into their blood, suggesting the immune system is behaving differently.

An In-Depth Exploration of the Autoantibody Immune Profile in ME/CFS Using Novel Antigen Profiling Techniques.

Germain, Arnaud, Jaycox, Jillian R, Emig, Christopher J et al.·International journal of molecular sciences·2025

This study looked for specific immune proteins called autoantibodies in the blood of ME/CFS patients to see if they might be causing the illness. Researchers tested over 7,500 different immune markers using advanced laboratory techniques in 172 people. Surprisingly, they did not find significant differences in autoantibodies between ME/CFS patients and healthy controls, though they did notice some subtle patterns between men and women with ME/CFS that warrant further investigation.

Killer cell immunoglobulin-like receptor (KIR) alleles suggested to be associated with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Ramadan, Donia Jamal, Kichula, Katherine M, Tao, Sudan et al.·Brain, behavior, and immunity·2025

This study examined specific genetic variations in natural killer (NK) cells—immune cells that help fight infections—in people with ME/CFS compared to healthy people. Researchers found that certain genetic variants were more common in ME/CFS patients while others were less common, suggesting that differences in how NK cells are regulated may play a role in ME/CFS. This supports the idea that immune system dysfunction is involved in the condition.

AI-driven multi-omics modeling of myalgic encephalomyelitis/chronic fatigue syndrome.

Xiong, Ruoyun, Aiken, Elizabeth, Caldwell, Ryan et al.·Nature medicine·2025

Researchers used artificial intelligence to analyze blood, gut bacteria, immune cells, and symptoms from 249 ME/CFS patients tracked over 4 years. The AI model discovered that ME/CFS involves abnormal patterns in gut bacteria products, blood fats, and immune cells that attack infections—particularly special T cells that become overactive. These findings suggest ME/CFS isn't caused by a single problem but by multiple connected systems going wrong together.

Temporal Dynamics of the Plasma Proteomic Landscape Reveals Maladaptation in ME/CFS Following Exertion.

Germain, Arnaud, Glass, Katherine A, Eckert, Melissa A et al.·Molecular & cellular proteomics : MCP·2025

Researchers studied what happens in the blood of ME/CFS patients during and after exercise to understand post-exertional malaise (PEM)—the worsening of symptoms that occurs after physical activity. They measured over 6,000 different proteins in 79 ME/CFS patients and 53 healthy controls before exercise, immediately after, and during recovery. They found that ME/CFS patients have abnormal protein changes during recovery that suggest their immune system and energy-producing cells are not working properly after exertion.

Abnormal T-Cell activation and cytotoxic T-Cell frequency discriminate symptom severity in myalgic encephalomyelitis/chronic fatigue syndrome.

Lee, Ji-Sook, Lacerda, Eliana, Kingdon, Caroline et al.·Journal of translational medicine·2025

This study compared immune system profiles in 96 ME/CFS patients with either mild/moderate or severe disease. Researchers found that people with severe ME/CFS had more activated immune cells and higher levels of inflammatory chemicals, while those with milder disease showed different patterns suggesting their bodies were responding to chronic viral infection. These findings suggest that mild and severe ME/CFS may involve different underlying immune problems, which could eventually help doctors predict disease severity and develop targeted treatments.

Functional and internalizing disorders co-aggregate with cardiometabolic and immune-related diseases within families: a population-based cohort study.

Steen, Olivier D, Bos, Martje, van Ockenburg, Sonja L et al.·BMC medicine·2025

This study found that ME/CFS, fibromyalgia, and irritable bowel syndrome tend to run in families alongside conditions like depression, anxiety, autoimmune diseases, and metabolic disorders. Researchers analyzed data from over 166,000 people in a Dutch population cohort to understand whether these conditions share common inherited risk factors. The findings suggest that the causes of functional disorders like ME/CFS may overlap with the causes of immune and metabolic diseases, which could point to new treatment approaches.

SMPDL3B a novel biomarker and therapeutic target in myalgic encephalomyelitis.

Rostami-Afshari, Bita, Elremaly, Wesam, Franco, Anita et al.·Journal of translational medicine·2025

Researchers identified a protein called SMPDL3B that appears to be elevated in people with ME/CFS and linked to symptom severity. This protein is found in the blood at higher levels in ME patients, particularly in women, and seems to be influenced by hormones and immune system dysfunction. The study also tested two existing diabetes medications (vildagliptin and saxagliptin) in the laboratory and found they could potentially help restore balance to this protein, suggesting a possible new treatment approach.

Immunological Patient Stratification in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Rohrhofer, Johanna, Hauser, Lisa, Lettenmaier, Lisa et al.·Journal of clinical medicine·2024

This study found that ME/CFS patients have different types of immune system problems. Researchers divided patients into two groups: those with weakened immune systems and those with normal immune systems. The two groups showed different patterns of illness—one group had low levels of a protective immune protein, while the other group had signs that their gut barrier was leaking. This suggests that ME/CFS may not be one disease but rather multiple conditions that need different treatment approaches.

Untargeted Metabolomics and Quantitative Analysis of Tryptophan Metabolites in Myalgic Encephalomyelitis Patients and Healthy Volunteers: A Comparative Study Using High-Resolution Mass Spectrometry.

Abujrais, Sandy, Vallianatou, Theodosia, Bergquist, Jonas·ACS chemical neuroscience·2024

Researchers compared blood chemistry between 38 people with ME/CFS and 24 healthy people to understand what might be different in their bodies. They found several chemical imbalances, particularly in how the body processes tryptophan (an amino acid) and in pathways related to energy production and inflammation. These differences suggest that ME/CFS patients may experience unusual immune activity and stress damage to their cells.

Data-independent LC-MS/MS analysis of ME/CFS plasma reveals a dysregulated coagulation system, endothelial dysfunction, downregulation of complement machinery.

Nunes, Massimo, Vlok, Mare, Proal, Amy et al.·Cardiovascular diabetology·2024

Researchers analyzed blood proteins in 15 ME/CFS patients and 10 healthy controls to look for differences that might explain ME/CFS symptoms. They found that ME/CFS patients had abnormal levels of proteins involved in blood clotting, blood vessel function, and immune system regulation. These findings suggest that problems with blood clotting and blood vessel health may play a role in ME/CFS.

Comparison of T-cell receptor diversity of people with myalgic encephalomyelitis versus controls.

Dibble, Joshua J, Ferneyhough, Ben, Roddis, Matthew et al.·BMC research notes·2024

Researchers studied immune cells called T-cells in people with ME/CFS to see if they were different from those in healthy people. They looked at genetic patterns in blood samples from 40 people in each group: those severely affected by ME/CFS, those mildly or moderately affected, people with multiple sclerosis, and healthy controls. Although they used advanced technology and computer programs to analyze the data, they found that the T-cell patterns were not notably different between the groups.

IgG Antibody Responses to Epstein-Barr Virus in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Their Effective Potential for Disease Diagnosis and Pathological Antigenic Mimicry.

Fonseca, André, Szysz, Mateusz, Ly, Hoang Thien et al.·Medicina (Kaunas, Lithuania)·2024

Researchers examined immune responses (antibodies) against Epstein-Barr virus in ME/CFS patients to see if these could be used to diagnose the condition. They found that a specific set of 26 antibodies could reliably identify ME/CFS patients whose illness started after an infection, but these antibodies don't appear to explain why the autoimmune problems occur. The findings suggest that while these antibodies might be useful for diagnosis in some patients, they may not be the root cause of ME/CFS.

Proteomics and cytokine analyses distinguish myalgic encephalomyelitis/chronic fatigue syndrome cases from controls.

Giloteaux, Ludovic, Li, Jiayin, Hornig, Mady et al.·Journal of translational medicine·2023

Researchers studied tiny particles called extracellular vesicles found in the blood of ME/CFS patients and compared them to healthy controls. They found that ME/CFS patients had more of these particles and they contained different levels of immune chemicals, particularly one called IL2. Using computer algorithms to analyze 20 different blood proteins, they could correctly identify ME/CFS patients about 86% of the time, suggesting that blood tests might one day help diagnose this condition.

Natural killer cytotoxicity in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a multi-site clinical assessment of ME/CFS (MCAM) sub-study.

Querec, Troy D, Lin, Jin-Mann S, Chen, Yang et al.·Journal of translational medicine·2023

Researchers tested whether a specific immune cell function called natural killer (NK) cytotoxicity could be a reliable blood test to help diagnose ME/CFS. They compared 174 people with ME/CFS to 86 healthy people and found no meaningful difference between the two groups. This means the test is not accurate enough to use in clinics right now, and scientists need to keep searching for better biological markers of ME/CFS.

A multicenter virome analysis of blood, feces, and saliva in myalgic encephalomyelitis/chronic fatigue syndrome.

Briese, Thomas, Tokarz, Rafal, Bateman, Lucinda et al.·Journal of medical virology·2023

Researchers looked for viruses in blood, saliva, and stool samples from ME/CFS patients and compared them to healthy people. They used advanced testing methods to search for viral genetic material but found no consistent differences between the two groups, except that ME/CFS patients had fewer anelloviruses (a common, typically harmless virus). This suggests that if viruses play a role in ME/CFS, the problem may not be the presence of the virus itself, but rather how the body's immune system responds to it.

Cytokine network analysis in a community-based pediatric sample of patients with myalgic encephalomyelitis/chronic fatigue syndrome.

Jason, Leonard A, Gaglio, Caroline L, Furst, Jacob et al.·Chronic illness·2023

Researchers studied immune system chemicals called cytokines in children and teens with ME/CFS by comparing blood samples from sick patients and healthy controls. They found that children with ME/CFS had different patterns of these immune chemicals compared to healthy kids, with certain inflammatory markers being more active. This suggests ME/CFS involves real biological changes in how the immune system works, particularly in severe cases.

Exploring the joint potential of inflammation, immunity, and receptor-based biomarkers for evaluating ME/CFS progression.

Berkis, Uldis, Svirskis, Simons, Krumina, Angelika et al.·Frontiers in immunology·2023

This study looked for blood markers that could help doctors understand how severe ME/CFS is and track disease progression. Researchers measured inflammation-related proteins, immune system components, and antibodies against nerve receptors in blood samples from healthy people and patients with mild, moderate, and severe ME/CFS. They found that certain markers—especially antibodies against beta2-adrenergic and M4 receptors, along with specific immune proteins—showed promise for distinguishing disease severity, with over 90% accuracy in identifying who has ME/CFS versus who is healthy.

The persistent viral infections in the development and severity of myalgic encephalomyelitis/chronic fatigue syndrome.

Rasa-Dzelzkaleja, Santa, Krumina, Angelika, Capenko, Svetlana et al.·Journal of translational medicine·2023

This study examined whether three common viruses—HHV-6, HHV-7, and parvovirus B19—play a role in ME/CFS by comparing 200 ME/CFS patients with 150 healthy people. The researchers found that ME/CFS patients were much more likely to have these viruses in an active state (replicating) rather than dormant, and those with active infections had higher levels of inflammatory markers. The severity of ME/CFS symptoms appeared linked to the presence and activity level of these viral infections.

Autoantibodies to selenoprotein P in chronic fatigue syndrome suggest selenium transport impairment and acquired resistance to thyroid hormone.

Sun, Qian, Oltra, Elisa, Dijck-Brouwer, D A Janneke et al.·Redox biology·2023

Some people with ME/CFS have antibodies that attack a protein called selenoprotein P, which normally helps transport selenium (a mineral needed for thyroid function) throughout the body. This study found that ME/CFS patients with these antibodies have lower selenium levels and struggle to convert thyroid hormone into its active form, which could explain why they feel tired and have other thyroid-like symptoms even when standard thyroid tests appear normal.

Survey of Anti-Pathogen Antibody Levels in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

O'Neal, Adam J, Glass, Katherine A, Emig, Christopher J et al.·Proteomes·2022

Researchers tested blood samples from ME/CFS patients to look for antibodies against 122 different germs that might trigger the illness. They compared the results to healthy people of similar age, sex, and weight. While they found differences in how men and women with ME/CFS respond to infections, they couldn't identify one specific germ as the culprit.

No replication of previously reported association with genetic variants in the T cell receptor alpha (TRA) locus for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Ueland, Marthe, Hajdarevic, Riad, Mella, Olav et al.·Translational psychiatry·2022

Researchers wanted to confirm whether certain genetic changes in a gene called TRA (involved in immune system function) were linked to ME/CFS, based on earlier findings. They tested this in large groups of people from Norway and the UK, but found that the genetic changes previously reported were not reliably associated with ME/CFS. While they found some other genetic variations that showed weak signals of association, none were strong enough to be considered genuine findings.

Comparative Analysis of Extracellular Vesicles in Patients with Severe and Mild Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Bonilla, Hector, Hampton, Dylan, Marques de Menezes, Erika G et al.·Frontiers in immunology·2022

Researchers looked for tiny particles called extracellular vesicles in the blood of people with ME/CFS to see if they could help diagnose or understand the disease. They found that people with severe ME/CFS had higher levels of certain vesicles that come from B cells (immune cells) and platelets (blood clotting cells) compared to healthy people. While these differences were promising, they weren't strong enough to confirm they're reliable markers yet.

Revisiting IgG Antibody Reactivity to Epstein-Barr Virus in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Its Potential Application to Disease Diagnosis.

Sepúlveda, Nuno, Malato, João, Sotzny, Franziska et al.·Frontiers in medicine·2022

This study looked at antibody responses to Epstein-Barr virus (EBV), a common virus linked to ME/CFS onset in some patients. Researchers analyzed blood samples from 92 ME/CFS patients and 50 healthy people, testing reactions to over 3,000 EBV proteins. They found that in patients whose ME/CFS started after a suspected EBV infection, two specific viral proteins triggered stronger antibody responses than in healthy controls. These antibody patterns could correctly identify about 83% of infected patients and 72% of healthy people, suggesting they might become useful diagnostic markers.

Biomarkers in the diagnostic algorithm of myalgic encephalomyelitis/chronic fatigue syndrome.

Gravelsina, Sabine, Vilmane, Anda, Svirskis, Simons et al.·Frontiers in immunology·2022

This study looked for biological markers (measurable signs in the blood) that could help doctors diagnose ME/CFS more easily. Researchers tested 134 ME/CFS patients and 33 healthy people for a virus called HHV-6 and specific antibodies that attack nerve receptors. They found that ME/CFS patients had higher levels of certain antibodies compared to healthy controls, and patients with more virus in their blood tended to have more severe symptoms.

Autoimmune gene expression profiling of fingerstick whole blood in Chronic Fatigue Syndrome.

Wang, Zheng, Waldman, Michelle F, Basavanhally, Tara J et al.·Journal of translational medicine·2022

Researchers tested blood samples from 166 ME/CFS patients and 83 healthy people to look for immune system clues that might explain the disease. They found that six specific genes related to immune function were more active in patients with severe, bedridden ME/CFS compared to those with milder disease. The study suggests these genes could potentially be used as biomarkers to identify how severe someone's ME/CFS is and might point toward new treatments.

Chronic Fatigue Exhibits Heterogeneous Autoimmunity Characteristics Which Reflect Etiology.

Danilenko, Olga V, Gavrilova, Natalia Y, Churilov, Leonid P·Pathophysiology : the official journal of the International Society for Pathophysiology·2022

This study found that ME/CFS patients have unusual immune system patterns—specifically, their bodies produce antibodies (immune proteins) that attack their own nervous system tissues. The researchers divided ME/CFS patients into three groups based on cause (viral infection, stress, or unknown origin) and found that different groups had different patterns of these self-attacking antibodies. Importantly, all ME/CFS patients showed elevated levels of antibodies against brain and nerve proteins, which could explain why the illness affects multiple body systems.

Systemic antibody responses against human microbiota flagellins are overrepresented in chronic fatigue syndrome patients.

Vogl, Thomas, Kalka, Iris N, Klompus, Shelley et al.·Science advances·2022

Researchers found that people with severe ME/CFS have different immune responses against bacteria in their gut compared to healthy people. Specifically, their blood contains more antibodies (immune proteins) that target flagella, which are whip-like structures used by certain gut bacteria to move. This immune signature was so distinctive that a computer algorithm could use it to help identify ME/CFS patients.

Clinical Heterogeneity in ME/CFS. A Way to Understand Long-COVID19 Fatigue.

Murga, Iñigo, Aranburu, Larraitz, Gargiulo, Pascual A et al.·Frontiers in psychiatry·2021

This study examined 84 ME/CFS patients and 22 healthy controls using questionnaires to measure fatigue, pain, sleep quality, heart rate problems, thinking difficulties, mood, and other symptoms. Researchers used statistical clustering to group patients into five distinct subtypes based on their symptom patterns. The findings suggest that ME/CFS is not one-size-fits-all—some patients have high anxiety and depression without fibromyalgia, while others have fibromyalgia combined with heart rate regulation problems, hormone imbalances, or immune issues.

Skewing of the B cell receptor repertoire in myalgic encephalomyelitis/chronic fatigue syndrome.

Sato, Wakiro, Ono, Hirohiko, Matsutani, Takaji et al.·Brain, behavior, and immunity·2021

This study looked at immune cells called B cells in people with ME/CFS and compared them to healthy people. The researchers found that ME/CFS patients have an unusual pattern of B cells—certain types are overrepresented while others are underrepresented. These abnormal B cell patterns were especially strong in patients whose ME/CFS started after an infection, suggesting the immune system may be stuck responding to something from that earlier infection.

Complement Component C1q as a Potential Diagnostic Tool for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Subtyping.

Castro-Marrero, Jesús, Zacares, Mario, Almenar-Pérez, Eloy et al.·Journal of clinical medicine·2021

Researchers analyzed blood samples from 250 women with ME/CFS to see if specific blood markers could help identify different types of the disease. They found that about 43% of participants had high levels of a protein called C1q, which was particularly associated with those experiencing more pain symptoms. This discovery suggests that blood tests might one day help doctors identify which ME/CFS patients belong to which subgroup, potentially leading to better tailored treatments.

Evaluation of Immune Dysregulation in an Austrian Patient Cohort Suffering from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Lutz, Lena, Rohrhofer, Johanna, Zehetmayer, Sonja et al.·Biomolecules·2021

This study looked at blood test results from 262 ME/CFS patients to understand problems with their immune systems. Researchers found that nearly two-thirds of patients had low levels of certain immune proteins or cells, while about one-quarter showed signs of inflammation. These findings suggest that immune system dysfunction is a common feature of ME/CFS and could potentially be used to help diagnose or treat the condition.

Recursive ensemble feature selection provides a robust mRNA expression signature for myalgic encephalomyelitis/chronic fatigue syndrome.

Metselaar, Paula I, Mendoza-Maldonado, Lucero, Li Yim, Andrew Yung Fong et al.·Scientific reports·2021

Researchers found a set of 23 genes in blood cells that could reliably identify people with ME/CFS. By looking at both gene activity and chemical markers on genes, they developed a test that correctly identified ME/CFS patients about 92-97% of the time. This is important because there's currently no reliable blood test to diagnose ME/CFS.

Fine mapping of the major histocompatibility complex (MHC) in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) suggests involvement of both HLA class I and class II loci.

Hajdarevic, Riad, Lande, Asgeir, Rekeland, Ingrid et al.·Brain, behavior, and immunity·2021

This study looked at genes related to the immune system in people with ME/CFS to understand why some people develop the condition. Researchers compared genetic markers in 427 Norwegian ME/CFS patients with 480 healthy controls and found two specific genetic regions associated with ME/CFS—one involving immune system genes that present antigens to cells, and another in a different immune region. These findings suggest the immune system's ability to recognize and respond to threats may play a role in ME/CFS.

Evaluating Routine Blood Tests According to Clinical Symptoms and Diagnostic Criteria in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Baklund, Ingrid H, Dammen, Toril, Moum, Torbjørn Åge et al.·Journal of clinical medicine·2021

Researchers compared blood test results from 149 ME/CFS patients with 264 healthy people to look for differences. They found that ME/CFS patients had higher levels of inflammation markers and certain blood cells, along with lower potassium and muscle enzyme levels. These differences suggest that ME/CFS may involve both inflammation and possible muscle or metabolic problems.

Are Circulating Fibroblast Growth Factor 21 and N-Terminal Prohormone of Brain Natriuretic Peptide Promising Novel Biomarkers in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome?

Domingo, Joan Carles, Cordobilla, Begoña, Ferrer, Roser et al.·Antioxidants & redox signaling·2021

This study looked for new blood markers that could help identify ME/CFS by measuring two proteins called FGF21 and NT-proBNP in patients and healthy people. The researchers found that ME/CFS patients had significantly higher levels of both proteins and showed signs of increased inflammation and oxidative stress (cellular damage). These findings suggest these proteins might be useful tools for diagnosing ME/CFS or developing new treatments.

Salivary DNA Loads for Human Herpesviruses 6 and 7 Are Correlated With Disease Phenotype in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Lee, Ji-Sook, Lacerda, Eliana M, Nacul, Luis et al.·Frontiers in medicine·2021

This study tested saliva samples from people with ME/CFS and healthy people to measure levels of common viruses that stay dormant in the body. Researchers found that two viruses (HHV-6B and HHV-7) were present at higher levels in people with ME/CFS, especially in those whose viral levels went up and down over time. Importantly, when these viral levels were higher, patients reported worse symptoms like pain, brain fog, and heart/blood pressure problems.

Sex-specific plasma lipid profiles of ME/CFS patients and their association with pain, fatigue, and cognitive symptoms.

Nkiliza, Aurore, Parks, Megan, Cseresznye, Adam et al.·Journal of translational medicine·2021

This study analyzed fatty substances in the blood of ME/CFS patients and healthy controls to see if they differ in ways that might explain symptoms. Researchers found that men and women with ME/CFS had different patterns of these blood fats compared to healthy people. Importantly, certain blood fats were connected to the severity of fatigue, headaches, and thinking difficulties, suggesting that problems with how the body processes fats may play a role in ME/CFS symptoms.

Hypothalamic-Pituitary Autoimmunity and Related Impairment of Hormone Secretions in Chronic Fatigue Syndrome.

De Bellis, Annamaria, Bellastella, Giuseppe, Pernice, Vlenia et al.·The Journal of clinical endocrinology and metabolism·2021

This study looked for specific immune system antibodies that attack the pituitary and hypothalamus—two small brain structures that control hormone production—in people with ME/CFS. Researchers found these antibodies in more than half of ME/CFS patients but none in healthy controls. Patients with these antibodies had lower levels of important hormones (like cortisol and growth hormone), and those with the highest antibody levels had the most severe ME/CFS symptoms.

Tryptophan Metabolites, Cytokines, and Fatty Acid Binding Protein 2 in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Simonato, Manuela, Dall'Acqua, Stefano, Zilli, Caterina et al.·Biomedicines·2021

This study compared blood samples from 40 people with ME/CFS to 40 healthy people to look for biological differences. Researchers found that ME/CFS patients had different levels of certain molecules related to immune function, gut health, and how the body uses the amino acid tryptophan. These differences were independent of each other, suggesting multiple biological pathways may be disrupted in ME/CFS.

Unravelling myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): Gender-specific changes in the microRNA expression profiling in ME/CFS.

Cheema, Amanpreet K, Sarria, Leonor, Bekheit, Mina et al.·Journal of cellular and molecular medicine·2020

This study looked at tiny molecules called microRNAs in the blood of people with ME/CFS to understand how their immune system responds to exercise. The researchers discovered that men and women with ME/CFS show different patterns in these molecules, and they also found that nutritional status affects these patterns. These findings could help explain why some people experience worsening symptoms after exercise (post-exertional malaise) and suggest that treatment approaches may need to differ between men and women.

The role of low-grade inflammation in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) - associations with symptoms.

Jonsjö, Martin A, Olsson, Gunnar L, Wicksell, Rikard K et al.·Psychoneuroendocrinology·2020

This study looked at whether low-level inflammation in the blood is connected to ME/CFS symptoms like exhaustion after activity, brain fog, muscle pain, and flu-like illness. Researchers tested 53 ME/CFS patients for various inflammatory markers and found that several of these markers were associated with cognitive problems and pain, though they were surprisingly less connected to post-exertional fatigue. Interestingly, the connection between inflammation and symptoms was different for men and women in some cases.

Deep phenotyping of myalgic encephalomyelitis/chronic fatigue syndrome in Japanese population.

Kitami, Toshimori, Fukuda, Sanae, Kato, Tamotsu et al.·Scientific reports·2020

Researchers studied 48 ME/CFS patients and 52 healthy people in Japan to find biological markers of the disease. They tested blood samples, gut bacteria, immune cells, and sleep patterns, identifying 26 potential markers that differ between patients and healthy people. Three markers stood out as most important: certain types of white blood cells, gut bacteria composition, and fat-like molecules in the blood, which were especially linked to sleep problems in ME/CFS patients.

Cytokine profiling of extracellular vesicles isolated from plasma in myalgic encephalomyelitis/chronic fatigue syndrome: a pilot study.

Giloteaux, Ludovic, O'Neal, Adam, Castro-Marrero, Jesús et al.·Journal of translational medicine·2020

This study looked at tiny particles called extracellular vesicles (EVs) in the blood of ME/CFS patients and compared them to healthy people. The researchers found that ME/CFS patients had more of these small particles, and the chemical messengers (cytokines) inside and around them showed unusual patterns of interaction that differed from healthy controls. This suggests that immune system signaling may be working differently in ME/CFS.

Human Leukocyte Antigen alleles associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Lande, Asgeir, Fluge, Øystein, Strand, Elin B et al.·Scientific reports·2020

Researchers studied immune system markers called HLA alleles in 426 Norwegian ME/CFS patients and compared them to healthy controls. They found that two specific immune markers (HLA-C*07:04 and HLA-DQB1*03:03) were more common in ME/CFS patients than in healthy people, suggesting the immune system may play a role in developing ME/CFS. About 1 in 5 ME/CFS patients carried one or both of these markers, compared to 1 in 8 healthy people.

Autoantibodies to beta-adrenergic and muscarinic cholinergic receptors in Myalgic Encephalomyelitis (ME) patients - A validation study in plasma and cerebrospinal fluid from two Swedish cohorts.

Bynke, Annie, Julin, Per, Gottfries, Carl-Gerhard et al.·Brain, behavior, & immunity - health·2020

Researchers tested blood and spinal fluid samples from ME/CFS patients and healthy people to look for certain antibodies (immune proteins) that mistakenly attack nerve receptors in the body. They found higher levels of some of these antibodies in ME/CFS patients compared to healthy controls, particularly antibodies targeting muscarinic receptors (involved in nerve signaling). However, the amount of these antibodies did not match how severe patients' symptoms were.

Identification of actin network proteins, talin-1 and filamin-A, in circulating extracellular vesicles as blood biomarkers for human myalgic encephalomyelitis/chronic fatigue syndrome.

Eguchi, Akiko, Fukuda, Sanae, Kuratsune, Hirohiko et al.·Brain, behavior, and immunity·2020

This study found that people with ME/CFS have higher levels of tiny particles called extracellular vesicles in their blood, which contain specific proteins (talin-1 and filamin-A) that appear to be unique markers of the disease. By measuring these particles and proteins in a simple blood test, researchers were able to correctly identify ME/CFS patients about 90-94% of the time, suggesting this could become a useful diagnostic tool.

Patients with ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) and chronic pain report similar level of sickness behavior as individuals injected with bacterial endotoxin at peak inflammation.

Jonsjö, Martin A, Åström, Jenny, Jones, Michael P et al.·Brain, behavior, & immunity - health·2020

This study compared how 'sick' people with ME/CFS and chronic pain feel compared to other groups. Researchers found that ME/CFS and chronic pain patients reported feeling as sick as healthy people who were given a bacterial toxin to trigger temporary inflammation. These high levels of sickness feelings were similar across both conditions and higher than what primary care patients reported, suggesting that the persistent sickness sensation in ME/CFS and chronic pain may involve similar biological mechanisms related to inflammation and how the brain processes illness signals.

Cytomegalovirus, Epstein-Barr virus, and human herpesvirus-6 infections in patients with myalgic еncephalomyelitis/chronic fatigue syndrome.

Shikova, Evelina, Reshkova, Valentina, Kumanova, Аntoniya et al.·Journal of medical virology·2020

Researchers tested 58 ME/CFS patients and 50 healthy people for three common viruses (EBV, CMV, and HHV-6) that have been suspected of triggering ME/CFS. They found that ME/CFS patients had significantly higher rates of active EBV infection in their bloodstream compared to healthy people, though most people in both groups carried these viruses in a dormant state. This suggests that for some patients, active EBV infection may play a role in ME/CFS development.

Assessing diagnostic value of microRNAs from peripheral blood mononuclear cells and extracellular vesicles in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Almenar-Pérez, Eloy, Sarría, Leonor, Nathanson, Lubov et al.·Scientific reports·2020

This study looked for biological markers (tiny genetic molecules called microRNAs) in blood samples from severely ill ME/CFS patients that could help doctors diagnose the disease. Researchers found that certain microRNAs and physical characteristics of particles in the blood appeared different in ME/CFS patients compared to healthy controls. If validated in larger studies, these findings could eventually lead to a simple blood test for diagnosis.

Changes in DNA methylation profiles of myalgic encephalomyelitis/chronic fatigue syndrome patients reflect systemic dysfunctions.

Helliwell, A M, Sweetman, E C, Stockwell, P A et al.·Clinical epigenetics·2020

This study looked at chemical tags on DNA called methylation patterns in people with ME/CFS compared to healthy people. These tags can turn genes on or off without changing the DNA itself. Researchers found that people with ME/CFS have different methylation patterns, particularly in genes related to energy production, immune function, and brain chemistry, which may help explain why they experience the symptoms they do.

Plasma proteomic profiling suggests an association between antigen driven clonal B cell expansion and ME/CFS.

Milivojevic, Milica, Che, Xiaoyu, Bateman, Lucinda et al.·PloS one·2020

Researchers studied blood proteins in ME/CFS patients and healthy controls to look for disease markers. They found that certain immune-related proteins, particularly immunoglobulin proteins (which are part of the immune system), were abnormal in ME/CFS patients and could help identify who has the disease. The results suggest ME/CFS involves an overactive or dysregulated immune response.

Peripheral endothelial dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome.

Scherbakov, Nadja, Szklarski, Marvin, Hartwig, Jelka et al.·ESC heart failure·2020

This study looked at blood vessel function in people with ME/CFS by measuring how well small arteries in the arm respond to increased blood flow. Researchers found that about half of ME/CFS patients had abnormal blood vessel responses, compared to only 20% of healthy people. People with this blood vessel problem reported more severe fatigue, more frequent need for rest breaks, and worse immune-related symptoms like sore throat and swollen lymph nodes.

Autoimmunity-Related Risk Variants in PTPN22 and CTLA4 Are Associated With ME/CFS With Infectious Onset.

Steiner, Sophie, Becker, Sonya C, Hartwig, Jelka et al.·Frontiers in immunology·2020

This study looked at specific genetic variations that are known to affect how the immune system works. Researchers compared DNA from ME/CFS patients and healthy controls, and found that certain genetic variations were more common in ME/CFS patients whose illness started with an infection. These genetic changes affect how immune cells are controlled, suggesting that autoimmunity may play a role specifically in ME/CFS cases that begin with an infection.

Whole blood human transcriptome and virome analysis of ME/CFS patients experiencing post-exertional malaise following cardiopulmonary exercise testing.

Bouquet, Jerome, Li, Tony, Gardy, Jennifer L et al.·PloS one·2019

Researchers gave ME/CFS patients and healthy controls exercise tests on two consecutive days, then tracked their blood samples for up to a week to look for signs of immune activation or virus reactivation during post-exertional malaise (PEM). Although ME/CFS patients felt significantly worse after exercise and some showed reduced oxygen use on day 2, blood tests revealed almost no differences in gene expression between patients and controls, and no evidence of viruses reactivating during PEM symptoms.

Changes in the transcriptome of circulating immune cells of a New Zealand cohort with myalgic encephalomyelitis/chronic fatigue syndrome.

Sweetman, Eiren, Ryan, Margaret, Edgar, Christina et al.·International journal of immunopathology and pharmacology·2019

Researchers studied blood immune cells from 10 ME/CFS patients and 10 healthy people to understand what's different at the genetic level. They found that several genes related to inflammation were more active in ME/CFS patients, and genes related to energy production and circadian rhythms (your body's internal clock) showed abnormal patterns. These findings suggest ME/CFS involves multiple biological systems working incorrectly at the same time.

Immunosignature Analysis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Günther, Oliver P, Gardy, Jennifer L, Stafford, Phillip et al.·Molecular neurobiology·2019

Researchers used a specialized test to examine antibodies (immune proteins) in the blood of people with ME/CFS and healthy controls. They found a pattern of 256 specific protein signatures in ME/CFS patients' blood that was different from healthy people. This suggests the immune system may be reacting to past infections in a way that could help doctors diagnose ME/CFS in the future.

Cellular Immune Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Cliff, Jacqueline M, King, Elizabeth C, Lee, Ji-Sook et al.·Frontiers in immunology·2019

This study examined the immune system of ME/CFS patients by testing their blood for signs of infection and measuring different types of immune cells. Researchers compared 251 ME/CFS patients (including 54 with severe ME/CFS) to healthy people and multiple sclerosis patients. They found that ME/CFS patients had unusual patterns in their T cells—a type of immune cell—but not in natural killer cells, contrary to what some earlier studies suggested.

Antibodies to Human Herpesviruses in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients.

Blomberg, Jonas, Rizwan, Muhammad, Böhlin-Wiener, Agnes et al.·Frontiers in immunology·2019

This study looked for evidence that common viruses called herpesviruses might be reactivated or causing problems in ME/CFS patients. Researchers tested blood samples from ME/CFS patients and healthy people to measure immune responses (antibodies) against several herpesviruses. While the overall antibody levels were similar between the two groups, the study found subtle differences in how ME/CFS patients' immune systems reacted to a few specific herpesvirus proteins.

Treatment Avenues in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Split-gender Pharmacogenomic Study of Gene-expression Modules.

Jeffrey, Mary G, Nathanson, Lubov, Aenlle, Kristina et al.·Clinical therapeutics·2019

Researchers studied blood samples from 33 ME/CFS patients and 21 healthy people to look for differences in how their genes were working. They found that ME/CFS appears to involve problems with the immune system (the body's defense mechanism) and how cells produce energy. By matching these gene differences with existing FDA-approved drugs, they identified immunosuppressant medications as potential candidates that might help reduce ME/CFS symptoms.

Searching for Serum Antibodies to Neuronal Proteins in Patients With Myalgic Encephalopathy/Chronic Fatigue Syndrome.

Giannoccaro, Maria Pia, Cossins, Judith, Sørland, Kari et al.·Clinical therapeutics·2019

Researchers tested blood samples from 50 ME/CFS patients and 50 healthy people to see if ME/CFS patients had unusual antibodies (immune proteins) that attack nerve cells. While a small number of both patients and healthy people had some immune activity toward nerve proteins, only one ME/CFS patient had a specific antibody that could be clearly identified. Interestingly, the patients who did have these antibodies tended to have more severe symptoms and had become ill more recently.

Associations between clinical symptoms, plasma norepinephrine and deregulated immune gene networks in subgroups of adolescent with Chronic Fatigue Syndrome.

Nguyen, Chinh Bkrong, Kumar, Surendra, Zucknick, Manuela et al.·Brain, behavior, and immunity·2019

This study looked at blood samples from teenagers with ME/CFS to understand how their immune systems and stress-response chemicals differ from healthy teenagers. Researchers found two distinct subgroups of ME/CFS patients based on immune activity and a stress hormone called norepinephrine. Patients with lower norepinephrine levels had more severe fatigue, while those with higher levels showed different patterns of immune dysfunction.

Rituximab Serum Concentrations and Anti-Rituximab Antibodies During B-Cell Depletion Therapy for Myalgic Encephalopathy/Chronic Fatigue Syndrome.

Rekeland, Ingrid G, Fluge, Øystein, Alme, Kine et al.·Clinical therapeutics·2019

This study looked at whether the amount of a drug called rituximab in patients' blood predicted whether they would improve from ME/CFS symptoms. The researchers measured rituximab levels in 23 patients and found no clear connection between how much drug was in the blood and who felt better. Interestingly, none of the patients developed antibodies against the drug, which was a potential concern.

Decreased Expression of the CD57 Molecule in T Lymphocytes of Patients with Chronic Fatigue Syndrome.

Espinosa, P, Urra, J M·Molecular neurobiology·2019

Researchers measured levels of a protein called CD57 on immune cells in ME/CFS patients and compared them to healthy people. They found that ME/CFS patients had significantly lower amounts of CD57 on their T cells (a type of white blood cell). This difference was large enough that measuring CD57 levels could potentially help doctors diagnose ME/CFS.

Increased risk of chronic fatigue syndrome following psoriasis: a nationwide population-based cohort study.

Tsai, Shin-Yi, Chen, Hsuan-Ju, Chen, Chi et al.·Journal of translational medicine·2019

This study found that people with psoriasis (a skin condition involving immune system dysfunction) have a higher chance of developing ME/CFS compared to people without psoriasis. Researchers followed over 13,000 people in Taiwan for several years and found that those with psoriasis were about 1.5 times more likely to develop ME/CFS. Interestingly, people who received certain psoriasis treatments appeared to have a lower risk of developing ME/CFS.

MicroRNAs as Biomarkers of Pain Intensity in Patients With Chronic Fatigue Syndrome.

Al-Rawaf, Hadeel A, Alghadir, Ahmad H, Gabr, Sami A·Pain practice : the official journal of World Institute of Pain·2019

This study looked at tiny molecules called microRNAs in the blood of adolescents with ME/CFS to see if they could help explain why these patients experience pain. Researchers found that five specific microRNAs were lower in ME/CFS patients compared to healthy teens, and these changes were linked to higher levels of inflammatory chemicals that are known to cause pain. Interestingly, girls with ME/CFS had even lower microRNA levels and higher inflammation markers than boys with the condition.

Genome-epigenome interactions associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Herrera, Santiago, de Vega, Wilfred C, Ashbrook, David et al.·Epigenetics·2018

This study examined how genes and chemical switches on genes (called methylation) work together in ME/CFS patients. Researchers compared immune cells from people with ME/CFS to healthy people, looking at hundreds of thousands of genetic markers and chemical modifications. They found that certain chemical switches on genes involved in immune function and energy production are different in ME/CFS patients, and these differences are connected to a person's genetic makeup.

Association of T and NK Cell Phenotype With the Diagnosis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Rivas, Jose Luis, Palencia, Teresa, Fernández, Guerau et al.·Frontiers in immunology·2018

This study compared immune system cells in the blood of people with ME/CFS to healthy people. Researchers found that ME/CFS patients had different levels of certain immune cells, particularly lower regulatory T cells and higher NKT-like cells, along with changes in natural killer (NK) cells. Using these immune cell differences, researchers could correctly identify about 70% of ME/CFS patients versus healthy controls, suggesting these immune markers might someday help doctors diagnose the condition.

Value of Circulating Cytokine Profiling During Submaximal Exercise Testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Moneghetti, Kegan J, Skhiri, Mehdi, Contrepois, Kévin et al.·Scientific reports·2018

Researchers tested whether measuring immune chemicals (called cytokines) in the blood after exercise could help identify people with ME/CFS. They compared 24 people with ME/CFS to 24 healthy controls and measured 51 different immune markers both before and 18 hours after exercise. They found that the pattern of immune chemicals measured 18 hours after exercise was different enough to reliably distinguish people with ME/CFS from healthy people.

Identification of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-associated DNA methylation patterns.

Trivedi, Malav S, Oltra, Elisa, Sarria, Leonor et al.·PloS one·2018

Researchers studied chemical tags on DNA (called methylation) in people with ME/CFS compared to healthy people. While the overall amount of these tags was similar between groups, they found specific locations on thousands of genes where the tags differed. Many of these differences were in genes involved in immune system function, which aligns with what doctors already know about ME/CFS affecting immunity.

Humoral Immunity Profiling of Subjects with Myalgic Encephalomyelitis Using a Random Peptide Microarray Differentiates Cases from Controls with High Specificity and Sensitivity.

Singh, Sahajpreet, Stafford, Phillip, Schlauch, Karen A et al.·Molecular neurobiology·2018

Researchers tested blood samples from 21 people with ME and 21 healthy controls to look for distinctive antibody patterns that could serve as a diagnostic test. Using a high-tech screening tool that checks for antibodies against thousands of different peptides, they found 25 unique patterns that could reliably distinguish people with ME from those without the disease. The antibodies appeared to target the person's own proteins and certain virus-like sequences found in human DNA.

Evaluation of four clinical laboratory parameters for the diagnosis of myalgic encephalomyelitis.

De Meirleir, Kenny L, Mijatovic, Tatjana, Subramanian, Krishnamurthy et al.·Journal of translational medicine·2018

Researchers tested four substances in the blood of 140 ME/CFS patients and 140 healthy people to see if they could help diagnose the disease. They found that three specific markers—sCD14, prostaglandin E2, and interleukin 8—were most useful for identifying ME/CFS. These findings suggest that a simple blood test might one day help doctors confirm ME/CFS diagnosis more quickly and objectively.

Longitudinal associations of lymphocyte subsets with clinical outcomes in chronic fatigue syndrome.

Mehalick, Melissa L, Schmaling, Karen B, Sabath, Daniel E et al.·Fatigue : biomedicine, health & behavior·2018

This study looked at how different types of immune cells (called lymphocytes) change over 18 months in people with ME/CFS and whether these changes connected to symptom severity and physical ability. Researchers tracked three types of immune cells in 93 ME/CFS patients and measured their fatigue, physical functioning, and energy levels over time. They found that certain immune cell patterns were linked to worse physical function and more symptoms, suggesting the immune system may play a role in ME/CFS severity.

Association between cytokines and psychiatric symptoms in chronic fatigue syndrome and healthy controls.

Groven, Nina, Fors, Egil A, Iversen, Valentina C et al.·Nordic journal of psychiatry·2018

This study looked at immune system markers called cytokines in people with ME/CFS compared to healthy people, and how these markers related to mood and anxiety symptoms. Researchers found that people with ME/CFS had slightly higher levels of one immune marker (TNF-α) and discovered different patterns of how immune markers connected to psychiatric symptoms in ME/CFS patients versus healthy controls. The findings suggest that immune system activity may work differently in ME/CFS, which could help explain some symptoms and guide future treatments.

Reduction of Glucocorticoid Receptor Function in Chronic Fatigue Syndrome.

Lynn, Megan, Maclachlan, Laura, Finkelmeyer, Andreas et al.·Mediators of inflammation·2018

This study looked at how the body's stress hormone system (glucocorticoid receptor) works in ME/CFS patients compared to healthy people. Researchers took blood samples and tested how well a stress hormone called dexamethasone could reduce inflammation markers. They found that ME/CFS patients had some differences in how their immune system responded, but the stress hormone system itself seemed to work similarly to healthy controls.

Hair and salivary cortisol in a cohort of women with chronic fatigue syndrome.

Roerink, Megan E, Roerink, Sean H P P, Skoluda, Nadine et al.·Hormones and behavior·2018

This study measured cortisol (a stress hormone) in hair and saliva samples from women with ME/CFS and compared them to healthy women. The ME/CFS patients showed lower cortisol levels, particularly a weaker morning cortisol rise. When some patients took a medication called anakinra (which reduces inflammation), their cortisol levels changed differently than in patients taking placebo, suggesting a link between the immune system and hormonal stress response in ME/CFS.

Depression, evening salivary cortisol and inflammation in chronic fatigue syndrome: A psychoneuroendocrinological structural regression model.

Milrad, Sara F, Hall, Daniel L, Jutagir, Devika R et al.·International journal of psychophysiology : official journal of the International Organization of Psychophysiology·2018

This study examined how depression, stress hormone levels, and inflammation connect in ME/CFS patients. Researchers found that people with ME/CFS who had higher evening cortisol (a stress hormone) levels also had more depression and higher levels of inflammatory markers in their blood. The results suggest that depression, hormones, and the immune system may be interconnected in ME/CFS, though more research is needed to understand which causes which.

Pitfalls in cytokine measurements - Plasma TGF-β1 in chronic fatigue syndrome.

Roerink, M E, van der Schaaf, M E, Hawinkels, L J A C et al.·The Netherlands journal of medicine·2018

This study measured a protein called TGF-β1 in the blood of ME/CFS patients compared to healthy people. Previous research suggested this protein was elevated in ME/CFS, but the researchers found that how blood samples are processed in the lab—specifically how fast they spin them—dramatically affects the results. When they carefully controlled this process, they found no actual difference in TGF-β1 levels between patients and healthy controls.

Novel characterisation of mast cell phenotypes from peripheral blood mononuclear cells in chronic fatigue syndrome/myalgic encephalomyelitis patients.

Nguyen, Thao, Johnston, Samantha, Chacko, Anu et al.·Asian Pacific journal of allergy and immunology·2017

This study looked at immune cells called mast cells in the blood of people with ME/CFS and compared them to healthy people. Researchers found that ME/CFS patients—especially those with severe illness—had more mast cells and these cells showed different activation patterns. Mast cells are known to release chemicals that cause inflammation, so understanding them better could help explain some ME/CFS symptoms.

Whole blood gene expression in adolescent chronic fatigue syndrome: an exploratory cross-sectional study suggesting altered B cell differentiation and survival.

Nguyen, Chinh Bkrong, Alsøe, Lene, Lindvall, Jessica M et al.·Journal of translational medicine·2017

This study looked at blood samples from 29 teenagers with ME/CFS and compared them to 18 healthy teens to see if their genes were working differently. The researchers found that certain immune cells involved in fighting infection were not developing or surviving normally in the ME/CFS group, and that signs of inflammation and antiviral activity were higher. These gene changes were connected to nervous system problems and symptoms like post-exertional malaise (feeling much worse after activity).

The UK ME/CFS Biobank for biomedical research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Multiple Sclerosis.

Lacerda, Eliana M, Bowman, Erinna W, Cliff, Jacqueline M et al.·Open journal of bioresources·2017

The UK ME/CFS Biobank is a collection of blood samples and health information from 284 people with ME/CFS, 60 people with multiple sclerosis, and 135 healthy volunteers. Researchers created this resource to help scientists study what causes ME/CFS and find better ways to diagnose and treat it. The samples and detailed patient information can be used by researchers worldwide to search for biological markers of the disease.

Epigenetic modifications and glucocorticoid sensitivity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

de Vega, Wilfred C, Herrera, Santiago, Vernon, Suzanne D et al.·BMC medical genomics·2017

This study looked at chemical tags attached to DNA in immune cells from ME/CFS patients and compared them to healthy people. Researchers found that ME/CFS patients had different patterns of these chemical tags, especially in genes related to how cells produce energy. Some of these differences were linked to patients' reported quality of life, suggesting that changes in how genes are regulated may contribute to ME/CFS symptoms.

Support for the microgenderome invites enquiry into sex differences.

Wallis, Amy, Butt, Henry, Ball, Michelle et al.·Gut microbes·2017

This study looked at how gut bacteria, sex hormones, and the immune system interact differently in men and women with ME/CFS. The researchers found that the relationship between specific types of bacteria in the gut and ME/CFS symptoms varies between males and females. This suggests that biological sex may play an important role in how the microbiome affects ME/CFS symptoms.

Immune network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome with atypical and classical presentations.

Hornig, M, Gottschalk, C G, Eddy, M L et al.·Translational psychiatry·2017

This study examined fluid from around the brain and spinal cord in people with ME/CFS to look for immune system differences. Researchers found that people whose ME/CFS started differently (without a clear infection trigger) had different patterns of immune molecules compared to those with typical ME/CFS that started after a viral-like illness. The atypical group had lower levels of certain inflammatory markers and less coordinated immune activity in their central nervous system.

Unperturbed Cytotoxic Lymphocyte Phenotype and Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients.

Theorell, Jakob, Bileviciute-Ljungar, Indre, Tesi, Bianca et al.·Frontiers in immunology·2017

Researchers tested whether immune cells called cytotoxic lymphocytes—which normally fight infections and respond to stress—work differently in ME/CFS patients compared to healthy people. They studied 48 ME/CFS patients and found that these immune cells looked and functioned normally, suggesting they are not responsible for ME/CFS symptoms. This means cytotoxic lymphocytes alone cannot be used as a simple blood test to diagnose the condition.

Activin B is a novel biomarker for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) diagnosis: a cross sectional study.

Lidbury, Brett A, Kita, Badia, Lewis, Donald P et al.·Journal of translational medicine·2017

Researchers tested blood samples from people with ME/CFS and compared them to healthy controls, looking for differences in proteins called activins. They found that people with ME/CFS had significantly higher levels of a protein called activin B, while activin A remained normal. This pattern could potentially be used as a blood test to help diagnose ME/CFS, since currently there is no reliable diagnostic test available.

Poor sleep quality is associated with greater circulating pro-inflammatory cytokines and severity and frequency of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) symptoms in women.

Milrad, Sara F, Hall, Daniel L, Jutagir, Devika R et al.·Journal of neuroimmunology·2017

This study looked at 60 women with ME/CFS to understand how sleep quality affects their symptoms and inflammation levels. Researchers found that women who slept poorly had higher levels of inflammatory substances in their blood and experienced more severe fatigue and ME/CFS symptoms. The findings suggest that improving sleep quality might help reduce both inflammation and symptom severity in people living with ME/CFS.

Cytokine responses to exercise and activity in patients with chronic fatigue syndrome: case-control study.

Clark, L V, Buckland, M, Murphy, G et al.·Clinical and experimental immunology·2017

This study examined whether people with ME/CFS have abnormal immune protein levels (cytokines) in their blood, especially after physical activity. Researchers compared 24 ME/CFS patients with 21 healthy controls and measured multiple immune markers at rest and after exercise. The study found no significant differences in immune protein levels between the two groups, and no link between post-exertional symptoms and increased cytokine levels.

Transforming growth factor beta (TGF-β) in adolescent chronic fatigue syndrome.

Wyller, Vegard Bruun, Nguyen, Chinh Bkrong, Ludviksen, Judith Anita et al.·Journal of translational medicine·2017

This study tested whether a protein called TGF-β, which helps regulate immune and stress responses, was elevated in adolescents with ME/CFS. Researchers compared blood levels of TGF-β in 120 young ME/CFS patients to 68 healthy controls and found the protein levels were actually the same in both groups. However, they discovered that in ME/CFS patients, TGF-β levels were connected to stress hormones and fatigue severity, suggesting it may play a role in how the illness affects the body even if it's not simply 'too high.'

Impact of Rantes from jawbone on Chronic Fatigue Syndrome.

Lechner, J, Huesker, K, Von Baehr, V·Journal of biological regulators and homeostatic agents·2017

This study investigated whether inflammation in the jawbone might contribute to ME/CFS. Researchers compared jawbone tissue from 21 ME/CFS patients with tissue from 19 healthy people and found that ME/CFS patients had significantly higher levels of inflammatory proteins (RANTES and FGF-2) in areas of jawbone that had undergone incomplete healing. The authors suggest that this hidden jawbone inflammation might be a previously unknown trigger for ME/CFS.

RNA-Seq Analysis of Gene Expression, Viral Pathogen, and B-Cell/T-Cell Receptor Signatures in Complex Chronic Disease.

Bouquet, Jerome, Gardy, Jennifer L, Brown, Scott et al.·Clinical infectious diseases : an official publication of the Infectious Diseases Society of America·2017

Researchers used genetic testing to compare blood samples from people with ME/CFS and a similar condition called alternative Lyme disease to healthy controls and people with lupus. They looked for differences in gene activity, immune cell patterns, and viral infections. Surprisingly, they found no major differences in gene activity between ME/CFS patients and healthy people, though they did find differences in lupus patients as expected.

Serological profiling of the EBV immune response in Chronic Fatigue Syndrome using a peptide microarray.

Loebel, Madlen, Eckey, Maren, Sotzny, Franziska et al.·PloS one·2017

This study examined whether ME/CFS patients have different immune responses to Epstein-Barr virus (EBV), a common virus that can cause mononucleosis. Researchers compared antibody patterns in 92 ME/CFS patients versus 50 healthy people and found that ME/CFS patients had slightly higher antibody levels against a specific EBV protein called EBNA-6. This suggests that some ME/CFS patients may have an altered immune response to EBV, though most antibody patterns were similar between patients and healthy controls.

Extended B cell phenotype in patients with myalgic encephalomyelitis/chronic fatigue syndrome: a cross-sectional study.

Mensah, F, Bansal, A, Berkovitz, S et al.·Clinical and experimental immunology·2016

Researchers compared immune cells called B cells in people with ME/CFS and healthy people using specialized lab tests. While they didn't find major differences in the most common B cell types, they did discover subtle changes in how B cells are marked and organized in ME/CFS patients, particularly an increase in certain markers on specific B cell subsets. These findings suggest B cells may function differently in ME/CFS and could help explain why some patients improve with a drug that targets B cells.

Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome.

Giloteaux, Ludovic, Goodrich, Julia K, Walters, William A et al.·Microbiome·2016

This study found that people with ME/CFS have different gut bacteria compared to healthy people. The bacteria in ME/CFS patients showed less diversity and included more potentially harmful species while having fewer beneficial ones. Additionally, researchers detected signs in the blood suggesting that bacteria or bacterial components may be leaking through the gut lining, which could contribute to inflammation and symptoms.

Genome-wide association analysis identifies genetic variations in subjects with myalgic encephalomyelitis/chronic fatigue syndrome.

Schlauch, K A, Khaiboullina, S F, De Meirleir, K L et al.·Translational psychiatry·2016

Researchers compared the genes of people with ME/CFS to healthy people and found 442 genetic differences that may be linked to the condition. While most of these differences were in non-coding parts of the genome, some were in actual genes that produce proteins, including two that change how proteins work. Some genetic differences were found in genes related to the immune system's T-cells, which fight infection.

Support for the Microgenderome: Associations in a Human Clinical Population.

Wallis, Amy, Butt, Henry, Ball, Michelle et al.·Scientific reports·2016

This study looked at gut bacteria in 274 ME/CFS patients and found that certain bacteria may affect symptoms differently in men and women, even when they have similar amounts of these bacteria. Specific bacteria called Firmicutes (including types like Clostridium and Lactobacillus) appeared connected to neurological, immune, and mood symptoms, but the way they affected symptoms depended on the patient's sex. This suggests that sex differences matter when understanding how gut bacteria influence ME/CFS.

Natural killer cells and single nucleotide polymorphisms of specific ion channels and receptor genes in myalgic encephalomyelitis/chronic fatigue syndrome.

Marshall-Gradisnik, Sonya, Huth, Teilah, Chacko, Anu et al.·The application of clinical genetics·2016

This study looked at immune cells called natural killer cells in ME/CFS patients and compared them to healthy controls. Researchers found that ME/CFS patients had weaker natural killer cell function and carried genetic variations in genes related to calcium regulation and nerve signal transmission. These genetic differences were not found in the healthy control group, suggesting they may play a role in ME/CFS.

Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome.

Landi, Abdolamir, Broadhurst, David, Vernon, Suzanne D et al.·Cytokine·2016

Researchers measured 34 different immune system proteins in blood samples from 100 ME/CFS patients and 79 healthy controls. They found that three specific immune proteins—IL-16, IL-7, and VEGF-A—were significantly lower in ME/CFS patients. This pattern was different from what is seen in other chronic diseases with similar fatigue symptoms, suggesting it may be unique to ME/CFS.

Association of biomarkers with health-related quality of life and history of stressors in myalgic encephalomyelitis/chronic fatigue syndrome patients.

Fenouillet, Emmanuel, Vigouroux, Aude, Steinberg, Jean Guillaume et al.·Journal of translational medicine·2016

This study examined blood markers and muscle function in 36 ME/CFS patients compared to 11 healthy controls to understand whether biological changes relate to symptoms and quality of life. Researchers found three key differences: problems with muscle response to exercise, increased oxidative stress (cellular damage), and changes in immune cells. These biomarkers correlated with how much ME/CFS affected patients' daily lives, especially in those whose illness started after a severe infection.

Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome.

Hornig, M, Gottschalk, G, Peterson, D L et al.·Molecular psychiatry·2016

Researchers examined fluid from around the spine (cerebrospinal fluid) in ME/CFS patients and compared it to healthy people and those with multiple sclerosis. They found that ME/CFS patients had unusual patterns of immune proteins called cytokines in this fluid, suggesting their immune system in the brain and spinal cord is activated differently. The most notable finding was higher levels of a protein called eotaxin, which typically helps recruit immune cells involved in allergic responses.

Illness progression in chronic fatigue syndrome: a shifting immune baseline.

Russell, Lindsey, Broderick, Gordon, Taylor, Renee et al.·BMC immunology·2016

This study looked at three inflammatory proteins (IL-1α, IL-6, and IL-8) in the blood of people with ME/CFS at different stages of illness—newly diagnosed teenagers, people in the middle of their illness, and those who had been sick for over a decade. The researchers found that the pattern of these proteins changes as the illness progresses, suggesting that the body's immune response shifts over time. By adjusting for how long someone has been ill, doctors might be able to use these three proteins together to identify ME/CFS with 75-88% accuracy.

ERK1/2, MEK1/2 and p38 downstream signalling molecules impaired in CD56 dim CD16+ and CD56 bright CD16 dim/- natural killer cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients.

Huth, Teilah Kathryn, Staines, Donald, Marshall-Gradisnik, Sonya·Journal of translational medicine·2016

This study looked at natural killer (NK) cells, which are immune cells that help fight infections and abnormal cells. Researchers found that NK cells in ME/CFS patients have problems with their internal signaling systems—the chemical pathways that tell these cells to attack threats. Specifically, certain types of NK cells showed abnormal activity in proteins called ERK, MEK, and p38 when compared to healthy people. These problems in cell signaling might explain why people with ME/CFS have weaker immune responses.

Single nucleotide polymorphisms and genotypes of transient receptor potential ion channel and acetylcholine receptor genes from isolated B lymphocytes in myalgic encephalomyelitis/chronic fatigue syndrome patients.

Marshall-Gradisnik, Sonya, Johnston, Samantha, Chacko, Anu et al.·The Journal of international medical research·2016

This small study looked at genetic differences in immune cells (B cells) from ME/CFS patients compared to healthy people. Researchers found that ME/CFS patients had more variations in genes controlling calcium flow and acetylcholine signaling—two processes important for immune cell communication. Some of these genetic variations were much more common in patients with ME/CFS, suggesting they might play a role in the disease.

Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome.

Loebel, Madlen, Grabowski, Patricia, Heidecke, Harald et al.·Brain, behavior, and immunity·2016

Researchers tested whether ME/CFS patients have unusually high levels of antibodies (immune proteins) that attack nerve signaling receptors in the body. They found that about 30% of ME/CFS patients had elevated antibodies against certain receptors involved in adrenaline and acetylcholine signaling—chemicals that control heart rate, breathing, and other automatic body functions. Importantly, patients who received rituximab (a treatment that depletes B cells) and improved showed decreases in these antibody levels, suggesting a possible link between these antibodies and disease activity.

Distinct plasma immune signatures in ME/CFS are present early in the course of illness.

Hornig, Mady, Montoya, José G, Klimas, Nancy G et al.·Science advances·2015

This study found that people with ME/CFS have distinctive patterns of immune system markers in their blood, but only early in the disease. Researchers compared blood samples from 52 people with early-stage ME/CFS to 348 healthy people and 246 people with long-standing ME/CFS. The early-stage group showed heightened immune activity that was not present in people who had been sick longer, suggesting the disease's immune profile changes over time.

A new case definition of Neuro-Inflammatory and Oxidative Fatigue (NIOF), a neuroprogressive disorder, formerly known as chronic fatigue syndrome or Myalgic Encephalomyelitis: results of multivariate pattern recognition methods and external validation by neuro-immune biomarkers.

Maes, Michael·Neuro endocrinology letters·2015

This study looked at whether ME/CFS could be better understood by examining specific blood markers related to inflammation, oxidative stress, and immune activation. Researchers found two distinct groups of people with chronic fatigue—one group had significantly higher levels of problematic immune markers and inflammatory signs. The study proposes a new way to identify ME/CFS based on fatigue plus at least four of these symptoms: muscle tension, memory problems, sleep issues, digestive problems, headaches, or flu-like feelings.

Increased expression of activation antigens on CD8+ T lymphocytes in Myalgic Encephalomyelitis/chronic fatigue syndrome: inverse associations with lowered CD19+ expression and CD4+/CD8+ ratio, but no associations with (auto)immune, leaky gut, oxidative and nitrosative stress biomarkers.

Maes, Michael, Bosmans, Eugene, Kubera, Marta·Neuro endocrinology letters·2015

This study examined immune cells called CD8+ T lymphocytes in ME/CFS patients and found they show higher levels of activation markers (CD38 and HLA-DR) compared to healthy people and those with regular fatigue. The researchers measured 139 ME/CFS patients, 65 with chronic fatigue, and 40 healthy controls, finding distinct immune patterns in ME/CFS that don't appear to be directly linked to inflammation, gut problems, or oxidative stress.

Serum Immune Proteins in Moderate and Severe Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients.

Hardcastle, Sharni Lee, Brenu, Ekua Weba, Johnston, Samantha et al.·International journal of medical sciences·2015

This study looked at immune system proteins in the blood of people with ME/CFS, comparing those with moderate and severe illness to healthy people. Researchers found that different immune markers were present at different levels depending on how severe someone's illness was. This suggests that ME/CFS may actually involve different immune patterns in different people, which could help researchers better understand why treatments don't work the same way for everyone.

Chronic fatigue syndrome: Features of a population of patients from northern Italy.

Capelli, E, Lorusso, L, Ghitti, M et al.·International journal of immunopathology and pharmacology·2015

This Italian study looked at medical records from 82 ME/CFS patients to understand what might trigger the illness and how it differs between men and women. Researchers found that patients who developed the condition at younger ages were more likely to have autoimmune problems (where the immune system attacks the body's own cells). The study also examined family members to see if certain events or conditions ran in families.

Cytokines in the cerebrospinal fluids of patients with chronic fatigue syndrome/myalgic encephalomyelitis.

Peterson, D, Brenu, E W, Gottschalk, G et al.·Mediators of inflammation·2015

Researchers tested cerebrospinal fluid (the fluid around the brain and spinal cord) from ME/CFS patients and healthy controls to see if immune chemicals called cytokines were different. Out of 27 different immune chemicals tested, they found that only one—called IL-10—was lower in ME/CFS patients. This suggests that immune system problems in the brain and nervous system may play a role in ME/CFS symptoms.

Longitudinal analysis of immune abnormalities in varying severities of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients.

Hardcastle, Sharni Lee, Brenu, Ekua Weba, Johnston, Samantha et al.·Journal of translational medicine·2015

This study tracked immune system changes in 42 ME/CFS patients (divided into moderate and severe groups) and 18 healthy controls over 6 months. Researchers used blood tests to count different types of immune cells. They found that people with severe ME/CFS had noticeably different immune cell patterns than those with moderate ME/CFS or healthy controls, suggesting the immune system may work differently depending on how severe the illness is.

Frequent IgG subclass and mannose binding lectin deficiency in patients with chronic fatigue syndrome.

Guenther, Sabrina, Loebel, Madlen, Mooslechner, Agnes A et al.·Human immunology·2015

This study looked at immune system proteins called antibodies and a molecule called mannose binding lectin (MBL) in 300 people with ME/CFS. The researchers found that about 25% of patients had lower-than-normal levels of certain antibodies, while another 25% had higher-than-normal levels. Additionally, 15% had low MBL levels, compared to only 6% in healthy people. These immune defects were connected to frequent respiratory infections in ME/CFS patients.

Pathway-focused genetic evaluation of immune and inflammation related genes with chronic fatigue syndrome.

Rajeevan, Mangalathu S, Dimulescu, Irina, Murray, Janna et al.·Human immunology·2015

Researchers compared the genes of 50 people with ME/CFS to 121 healthy people to look for differences in genes related to immune system and inflammation. They found 32 genetic differences associated with ME/CFS, particularly in genes controlling how the body's natural defense system works. These findings suggest that problems with immune activation may play a role in ME/CFS.

Plasma cytokine expression in adolescent chronic fatigue syndrome.

Wyller, Vegard Bruun, Sørensen, Øystein, Sulheim, Dag et al.·Brain, behavior, and immunity·2015

This study measured inflammation markers called cytokines in the blood of 120 adolescents with ME/CFS and compared them to 68 healthy young people. Despite CFS patients reporting significantly more fatigue and symptoms suggesting inflammation, the researchers found no differences in cytokine levels or inflammation patterns between the two groups. This suggests that the fatigue and symptoms in adolescent ME/CFS may not be caused by the type of low-grade inflammation in the blood that researchers had previously suspected.

Polymorphism in COMT is associated with IgG3 subclass level and susceptibility to infection in patients with chronic fatigue syndrome.

Löbel, Madlen, Mooslechner, Agnes Anna, Bauer, Sandra et al.·Journal of translational medicine·2015

This study looked at a genetic variation in a gene called COMT that affects how the body handles stress hormones. Researchers compared 74 ME/CFS patients with 76 healthy people and found that ME/CFS patients with a specific genetic variant (Met/Met) had higher stress hormone levels, weaker immune responses to certain infections, and got respiratory infections more often. This suggests that a person's genes may influence both their stress response and infection risk in ME/CFS.

Increased Risk of Chronic Fatigue Syndrome Following Atopy: A Population-Based Study.

Yang, Tse-Yen, Kuo, Haung-Tsung, Chen, Hsuan-Ju et al.·Medicine·2015

This study tracked over 200,000 people for 4-6 years to see if allergies and atopic conditions (like asthma, eczema, and hay fever) increase the risk of developing ME/CFS. People with atopy were 1.5 times more likely to develop ME/CFS than those without atopy, and the risk was even higher for people with multiple atopic conditions. This suggests a possible link between the body's allergic responses and the development of ME/CFS.

Evidence for the existence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) with and without abdominal discomfort (irritable bowel) syndrome.

Maes, Michael, Leunis, Jean-Claude, Geffard, Michel et al.·Neuro endocrinology letters·2014

This study found that many people with ME/CFS experience stomach and digestive problems, and this appears to be linked to bacteria from the gut leaking into the bloodstream. Researchers identified two groups of ME/CFS patients: those with significant abdominal discomfort and those without. The group with digestive symptoms showed higher levels of immune responses to gut bacteria, suggesting their intestinal barrier may be more permeable.

Attenuation of autoimmune responses to oxidative specific epitopes, but not nitroso-adducts, is associated with a better clinical outcome in Myalgic Encephalomyelitis/chronic fatigue syndrome.

Maes, Michael, Leunis, Jean-Claude·Neuro endocrinology letters·2014

This study looked at whether certain harmful substances in the blood of ME/CFS patients were linked to how sick they felt. Researchers gave 76 patients with ME/CFS supplements designed to reduce inflammation and oxidative stress, and found that patients whose levels of these harmful substances decreased the most—particularly those related to fat oxidation—reported feeling better. However, another type of harmful substance (related to nitrosative stress) didn't show this same connection to improvement.

Role of adaptive and innate immune cells in chronic fatigue syndrome/myalgic encephalomyelitis.

Brenu, Ekua Weba, Huth, Teilah K, Hardcastle, Sharni L et al.·International immunology·2014

This study compared immune system cells in 30 people with ME/CFS and 25 healthy controls to identify which immune cells are abnormal in ME/CFS. Researchers found several key differences: patients with ME/CFS had unusual numbers and activity levels of immune cells called B cells, regulatory T cells, and neutrophils. These findings suggest that ME/CFS involves problems with how the immune system regulates itself, similar to autoimmune diseases.

Dimensions of pure chronic fatigue: psychophysical, cognitive and biological correlates in the chronic fatigue syndrome.

Neu, Daniel, Mairesse, Olivier, Montana, Xavier et al.·European journal of applied physiology·2014

This study compared 16 people with ME/CFS to 14 healthy controls to understand fatigue better. Researchers measured attention, reaction time, muscle strength, sleep patterns, and immune markers (cytokines). They found that people with ME/CFS had cognitive problems, slower reactions, weaker grip strength, and higher levels of certain inflammatory markers—but their sleep time was actually similar to controls.

In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation.

Maes, Michael, Ringel, Karl, Kubera, Marta et al.·Journal of affective disorders·2013

This study found that people with ME/CFS often develop antibodies (immune proteins) against serotonin, a chemical messenger in the brain. These antibodies were linked to higher levels of inflammation, signs of bacteria leaking from the gut, and worse symptoms including pain, fatigue, brain fog, and mood changes. The findings suggest ME/CFS involves immune system problems that may contribute to the condition's core symptoms.

Epitopes of microbial and human heat shock protein 60 and their recognition in myalgic encephalomyelitis.

Elfaitouri, Amal, Herrmann, Björn, Bölin-Wiener, Agnes et al.·PloS one·2013

This study looked at whether ME/CFS patients have different immune responses to heat shock protein 60 (HSP60), a protein found in both human cells and bacteria. Researchers tested blood samples from ME/CFS patients and healthy people, finding that some ME/CFS patients had specific antibodies against a bacterial version of this protein. This suggests that a past infection might trigger the immune system to attack proteins in the body, which could contribute to ME/CFS.

Altered functional B cell subset populations in patients with chronic fatigue syndrome compared to healthy controls.

Bradley, A S, Ford, B, Bansal, A S·Clinical and experimental immunology·2013

This study looked at different types of B cells (immune cells that help fight infection) in people with ME/CFS compared to healthy people. Researchers found that ME/CFS patients had more immature B cells and fewer fully developed B cells than healthy controls, suggesting their immune system might not be developing B cells normally. This finding is interesting because a drug that removes B cells helped some ME/CFS patients improve.

Screening NK-, B- and T-cell phenotype and function in patients suffering from Chronic Fatigue Syndrome.

Curriu, Marta, Carrillo, Jorge, Massanella, Marta et al.·Journal of translational medicine·2013

This study examined the immune cells in the blood of 22 people with ME/CFS and 30 healthy controls using a technique called flow cytometry. Researchers found that people with ME/CFS had some notable differences in their T cells and NK cells—types of white blood cells that help fight infections—while B cells appeared largely normal. These immune cell differences may help doctors identify ME/CFS and might explain why people with the condition get frequent viral infections.

Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology.

Stringer, Elizabeth Ann, Baker, Katharine Susanne, Carroll, Ian R et al.·Journal of translational medicine·2013

This study tracked blood samples and fatigue reports from 10 people with ME/CFS and 10 healthy people over 25 days. Researchers found that a hormone called leptin—which controls hunger and immune function—was linked to daily changes in fatigue severity in people with ME/CFS. A computer program analyzing all measured immune markers could correctly identify high fatigue days versus low fatigue days about 78% of the time, suggesting the immune system plays a real role in ME/CFS symptoms.

Human endogenous retrovirus-K18 superantigen expression and human herpesvirus-6 and human herpesvirus-7 viral loads in chronic fatigue patients.

Oakes, Brendan, Hoagland-Henefield, Matthias, Komaroff, Anthony L et al.·Clinical infectious diseases : an official publication of the Infectious Diseases Society of America·2013

Researchers tested whether two common viruses (HHV-6 and HHV-7) and a genetic element called HERV-K18 were present at higher levels in people with ME/CFS compared to healthy controls. They measured these in blood and saliva samples from 39 ME/CFS patients and 9 healthy people. They found no significant differences between the two groups, and these markers did not correlate with how severe patients' symptoms were.

Myalgic Encephalomyelitis (ME), Chronic Fatigue Syndrome (CFS), and Chronic Fatigue (CF) are distinguished accurately: results of supervised learning techniques applied on clinical and inflammatory data.

Maes, Michael, Twisk, Frank N M, Johnson, Cort·Psychiatry research·2012

This study looked at whether ME, CFS, and chronic fatigue are truly different conditions or if they overlap too much to distinguish. Researchers tested 144 patients and found that post-exertional malaise (PEM)—where symptoms worsen after activity—is a key feature that separates ME from CFS. They also found that ME and CFS patients had higher levels of certain inflammatory markers in their blood compared to people with simple chronic fatigue.

Evidence for inflammation and activation of cell-mediated immunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): increased interleukin-1, tumor necrosis factor-α, PMN-elastase, lysozyme and neopterin.

Maes, Michael, Twisk, Frank N M, Kubera, Marta et al.·Journal of affective disorders·2012

This study examined whether people with ME/CFS have higher levels of inflammatory markers—substances in the blood that signal inflammation—compared to healthy people and those with regular fatigue. Researchers found that ME/CFS patients had significantly elevated levels of five different inflammatory markers, and these markers were linked to common ME/CFS symptoms like fatigue, brain fog, and flu-like feelings. The findings suggest that low-grade inflammation in the body may be contributing to ME/CFS symptoms.

IgM-mediated autoimmune responses directed against anchorage epitopes are greater in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) than in major depression.

Maes, Michael, Mihaylova, Ivana, Kubera, Marta et al.·Metabolic brain disease·2012

This study examined immune system markers in people with ME/CFS, depression, and healthy controls. Researchers found that people with ME/CFS had higher levels of specific immune antibodies (IgM) attacking certain body molecules compared to people with depression. These antibodies were especially high against fatty acid anchors and oxidatively damaged proteins, suggesting ME/CFS may involve distinct immune processes that differ from depression.

Inflammatory and cell-mediated immune biomarkers in myalgic encephalomyelitis/chronic fatigue syndrome and depression: inflammatory markers are higher in myalgic encephalomyelitis/chronic fatigue syndrome than in depression.

Maes, Michael, Twisk, Frank N M, Ringel, Karl·Psychotherapy and psychosomatics·2012

This study found that people with ME/CFS have higher levels of inflammatory markers (immune chemicals) in their blood compared to people with depression, even though both conditions can cause fatigue and other similar symptoms. The researchers measured specific immune proteins and found that while both ME/CFS and depression involve some immune system changes, ME/CFS shows a distinctly different immune profile that helps distinguish it from depression.

Increased IgA responses to the LPS of commensal bacteria is associated with inflammation and activation of cell-mediated immunity in chronic fatigue syndrome.

Maes, Michael, Twisk, Frank N M, Kubera, Marta et al.·Journal of affective disorders·2012

This study found that people with ME/CFS have higher levels of immune antibodies (IgA) that react to bacteria normally living in their gut. These elevated antibodies were connected to increased inflammation and immune system activation in the blood. The more of these antibodies patients had, the worse their symptoms—including fatigue, brain fog, and digestive problems—tended to be.

Association of active human herpesvirus-6, -7 and parvovirus b19 infection with clinical outcomes in patients with myalgic encephalomyelitis/chronic fatigue syndrome.

Chapenko, Svetlana, Krumina, Angelika, Logina, Inara et al.·Advances in virology·2012

This study tested 108 ME/CFS patients and 90 healthy people for three viruses: HHV-6, HHV-7, and parvovirus B19. The researchers found that about 65% of ME/CFS patients had active viral infections compared to only 13% of healthy people. Patients with active viral infections showed higher levels of inflammatory markers and experienced more severe symptoms, especially when infected with multiple viruses at once.

Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis.

Brenu, Ekua W, van Driel, Mieke L, Staines, Donald R et al.·Journal of translational medicine·2012

This study tracked immune system changes in 65 people with ME/CFS over one year, comparing them to 21 healthy controls. Researchers found that people with ME/CFS had consistently lower natural killer (NK) cell activity—immune cells that help fight infections—throughout the year. They also found changes in inflammatory molecules called cytokines that fluctuated at different time points.

Predictors of Fatigue among Patients with Chronic Fatigue Syndrome.

Jason, Leonard A, Brown, Molly, Evans, Meredyth et al.·Journal Of Human Behavior In The Social Environment·2012

This study asked ME/CFS patients to keep detailed activity logs to understand what triggers their fatigue. Researchers looked at what patients were doing, what they had been doing 30 minutes earlier, and their fatigue levels to find patterns. The study suggests that tracking daily activities can help doctors and patients see which activities are most connected to fatigue flare-ups.

No serological evidence for a role of HHV-6 infection in chronic fatigue syndrome.

Burbelo, Peter D, Bayat, Ahmad, Wagner, Jason et al.·American journal of translational research·2012

This study tested whether a virus called HHV-6 might be causing chronic fatigue syndrome (ME/CFS). Researchers compared antibodies (immune system markers) against HHV-6 in people with ME/CFS and healthy controls. They found that both groups had similar levels of HHV-6 antibodies, suggesting this virus is unlikely to be a major cause of ME/CFS.

Stress management skills, neuroimmune processes and fatigue levels in persons with chronic fatigue syndrome.

Lattie, Emily G, Antoni, Michael H, Fletcher, Mary Ann et al.·Brain, behavior, and immunity·2012

This study looked at whether people with ME/CFS who are better at managing stress have lower fatigue levels. Researchers measured stress management skills, emotional distress, fatigue, and inflammation markers in the blood and saliva of 117 people with ME/CFS. They found that people with better stress management skills reported less fatigue and emotional distress, and this benefit was especially strong in people who had higher levels of a specific inflammatory marker called IL-6.

Differences in metabolite-detecting, adrenergic, and immune gene expression after moderate exercise in patients with chronic fatigue syndrome, patients with multiple sclerosis, and healthy controls.

White, Andrea T, Light, Alan R, Hughen, Ronald W et al.·Psychosomatic medicine·2012

This study compared how the bodies of ME/CFS patients, multiple sclerosis (MS) patients, and healthy people respond to moderate exercise by measuring changes in specific genes in blood cells. ME/CFS patients experienced much larger increases in fatigue and pain after exercise, and showed distinctive patterns of gene activity related to pain sensing and stress hormones that were different from MS patients and healthy controls.

Humoral and cellular immune responses after influenza vaccination in patients with chronic fatigue syndrome.

Prinsen, Hetty, de Vries, I Jolanda M, Torensma, Ruurd et al.·BMC immunology·2012

This study tested how well people with ME/CFS respond to the flu vaccine compared to healthy people. Researchers measured both antibody production (humoral immunity) and T cell activity (cellular immunity) before and after vaccination. The results showed that people with ME/CFS had immune responses to the flu vaccine that were similar to healthy controls, suggesting their immune systems can respond normally to this vaccine.

Response to valganciclovir in chronic fatigue syndrome patients with human herpesvirus 6 and Epstein-Barr virus IgG antibody titers.

Watt, Tessa, Oberfoell, Stephanie, Balise, Raymond et al.·Journal of medical virology·2012

This study looked at whether a antiviral medication called valganciclovir could help ME/CFS patients who had high levels of antibodies to two common viruses: HHV-6 and EBV. Sixty-one patients took the medication for varying lengths of time, and about half reported at least 30% improvement in their physical energy and thinking abilities. Interestingly, the improvement didn't depend on how high their antibody levels were at the start—patients improved simply from taking the medication, and those who took it longer did better.

Chronic fatigue syndrome and subsequent risk of cancer among elderly US adults.

Chang, Cindy M, Warren, Joan L, Engels, Eric A·Cancer·2012

Researchers investigated whether people with ME/CFS have a higher risk of developing cancer. Using medical records from over 1.2 million elderly Americans, they found that people with ME/CFS had a slightly increased risk of non-Hodgkin lymphoma (a blood cancer), particularly certain subtypes. The study does not prove that ME/CFS causes cancer, but suggests that shared immune system problems or infections might explain the connection.

Benefit from B-Lymphocyte Depletion Using the Anti-CD20 Antibody Rituximab in Chronic Fatigue Syndrome

Øystein Fluge, Olav Mella, Ove Bruland et al.·PLoS ONE·2011·n=30

In this pilot RCT, 30 ME/CFS patients received rituximab (a B-cell depleting antibody used in cancer and autoimmune disease) or placebo. Two-thirds of the rituximab group showed clinical improvement, with delayed response patterns consistent with autoimmune disease mechanisms. The placebo group had minimal response.

Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis.

Brenu, Ekua W, van Driel, Mieke L, Staines, Don R et al.·Journal of translational medicine·2011

This study examined immune system markers in 95 ME/CFS patients compared to 50 healthy people to see if certain blood tests could help diagnose the condition. Researchers found that ME/CFS patients had imbalanced immune responses, including higher levels of certain inflammatory proteins and lower activity of immune cells that normally fight infections. These immune differences might one day be used as reliable diagnostic markers to help doctors identify ME/CFS.

Diagnostic accuracy of symptoms characterising chronic fatigue syndrome.

Davenport, Todd E, Stevens, Staci R, Baroni, Katie et al.·Disability and rehabilitation·2011

This study looked at which symptoms best identify people with ME/CFS by comparing 16 patients with the condition to 14 healthy controls. The researchers found that failure to recover within one day after intense exercise was the strongest single indicator of ME/CFS, and combining three symptoms—immune problems, sleep disturbance, and pain—could accurately identify most patients. The findings suggest that fewer symptoms may be needed to diagnose ME/CFS than current guidelines require.

Investigation into the presence of and serological response to XMRV in CFS patients.

Erlwein, Otto, Robinson, Mark J, Kaye, Steve et al.·PloS one·2011

This study tested whether a virus called XMRV could be found in people with ME/CFS. Researchers used the same methods from earlier studies that had suggested a link between this virus and ME/CFS. They checked patient blood samples for the virus itself and for antibodies (immune response markers) to the virus. Their results found no evidence that XMRV is associated with ME/CFS in UK patients.

Up-regulation of TGF-β1 mRNA expression in peripheral blood mononuclear cells of patients with chronic fatigue syndrome.

Zhang, Hai-Ying, Liu, Zhan-Dong, Hu, Chao-Jun et al.·Journal of the Formosan Medical Association = Taiwan yi zhi·2011

Researchers measured levels of a immune signaling molecule called TGF-β1 in blood cells from ME/CFS patients and compared them to healthy people and patients with other illnesses. They found that ME/CFS patients had significantly higher levels of TGF-β1 than both groups, suggesting this molecule may play a role in ME/CFS disease development.

Fatigue, depressive symptoms, and anxiety from adolescence up to young adulthood: a longitudinal study.

ter Wolbeek, Maike, van Doornen, Lorenz J P, Kavelaars, Annemieke et al.·Brain, behavior, and immunity·2011

This study followed 633 teenage girls for 4.5 years to understand what causes fatigue and ME/CFS-like symptoms in young adulthood. Researchers found that fatigue, depression, and anxiety tend to rise and fall together over time, and that certain immune markers and emotional problems during teenage years could predict who would develop fatigue later. The study suggests that warning signs of future fatigue can sometimes be spotted years before symptoms become serious.

Excess of activating killer cell immunoglobulin‑like receptors and lack of HLA-Bw4 ligands: a two‑edged weapon in chronic fatigue syndrome.

Pasi, Annamaria, Bozzini, Sara, Carlo-Stella, Nicoletta et al.·Molecular medicine reports·2011

This study examined immune system genes called KIRs and their matching partners (HLA molecules) in people with ME/CFS. Researchers found that people with ME/CFS had an unusual pattern of these immune genes—specifically, more of a type called KIR3DS1 and fewer matching HLA partners for their receptors to recognize. The researchers suggest this mismatch might make it harder for the immune system to fight off infections, potentially allowing chronic infections to persist.

Immunologic and psychosocial status in chronic fatigue syndrome.

Nas, K, Cevik, R, Batum, S et al.·Bratislavske lekarske listy·2011

Researchers compared immune system markers and psychological health in 25 ME/CFS patients and 20 healthy controls. They found that ME/CFS patients had lower levels of a specific type of immune cell (CD56) and higher levels of an inflammatory marker (IL-6), along with more depression and reduced quality of life. These immune changes appeared connected to sleep problems, social isolation, and physical limitations.

An unbiased metagenomic search for infectious agents using monozygotic twins discordant for chronic fatigue.

Sullivan, Patrick F, Allander, Tobias, Lysholm, Fredrik et al.·BMC microbiology·2011

Researchers used advanced genetic sequencing to search for viruses in the blood of 45 people with chronic fatigue syndrome, comparing each patient to their identical twin who did not have the illness. They found that a virus called GB virus C appeared in a few patients but not in their healthy twins, suggesting it might be linked to ME/CFS. However, the overall results did not strongly support the idea that a single detectable virus causes chronic fatigue.

Xenotropic murine leukemia virus-related virus-associated chronic fatigue syndrome reveals a distinct inflammatory signature.

Lombardi, Vincent C, Hagen, Kathryn S, Hunter, Kenneth W et al.·In vivo (Athens, Greece)·2011

This 2011 study looked for a specific virus (XMRV) in the blood of ME/CFS patients and measured immune system chemicals called cytokines and chemokines. Researchers found a distinctive pattern of 10 immune chemicals that could identify XMRV-positive patients with very high accuracy (93-96%), suggesting that this virus may trigger a particular type of immune response in some people with ME/CFS.

Unravelling the nature of postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: the role of elastase, complement C4a and interleukin-1beta.

Nijs, J, Van Oosterwijck, J, Meeus, M et al.·Journal of internal medicine·2010

This study looked at what happens in the blood after people with ME/CFS exercise. Researchers compared 22 women with ME/CFS to 22 healthy women and measured specific immune markers (elastase, IL-1beta, and complement C4a) before and after two different types of exercise. Both types of exercise triggered postexertional malaise (a worsening of symptoms after activity) in the ME/CFS group, but surprisingly, the immune markers they measured didn't show significant changes in either group.

Microbial infections in eight genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis.

Zhang, Lihan, Gough, John, Christmas, David et al.·Journal of clinical pathology·2010

This study looked at blood samples from ME/CFS patients to identify different genetic subtypes based on how 88 genes were turned on or off. Researchers found that ME/CFS patients had distinct genetic patterns that were different from healthy people and those with depression. They also discovered that different viral infections—particularly Epstein-Barr virus and enterovirus—were linked to different genetic subtypes of ME/CFS.

Antibody to parvovirus B19 nonstructural protein is associated with chronic arthralgia in patients with chronic fatigue syndrome/myalgic encephalomyelitis.

Kerr, Jonathan R, Gough, John, Richards, Selwyn C M et al.·The Journal of general virology·2010

This study looked at whether parvovirus B19 (a common virus) plays a role in ME/CFS, particularly in patients with joint pain. While ME/CFS patients and healthy people had similar rates of past B19 infection, researchers found that ME/CFS patients were much more likely to have specific antibodies suggesting the virus wasn't being cleared properly from their body. Interestingly, patients with these antibodies were more likely to report chronic joint pain.

Biochemical and vascular aspects of pediatric chronic fatigue syndrome.

Kennedy, Gwen, Khan, Faisel, Hill, Alexander et al.·Archives of pediatrics & adolescent medicine·2010

This study compared 25 children with ME/CFS to 23 healthy children to understand what happens in their bodies at a chemical and blood vessel level. The researchers found that children with ME/CFS had signs of increased oxidative stress (cellular damage from harmful molecules) and more dying white blood cells, similar to what has been seen in adults with ME/CFS. However, unlike adults, the children's blood vessel stiffness appeared normal.

Xenotropic murine leukemia virus-related virus prevalence in patients with chronic fatigue syndrome or chronic immunomodulatory conditions.

Henrich, Timothy J, Li, Jonathan Z, Felsenstein, Donna et al.·The Journal of infectious diseases·2010

Researchers tested whether a virus called XMRV was present in people with ME/CFS and other conditions affecting the immune system. They collected samples from 293 patients, including 32 with ME/CFS, and looked for XMRV DNA. They found no evidence of this virus in any of the samples tested.

Biomarkers in chronic fatigue syndrome: evaluation of natural killer cell function and dipeptidyl peptidase IV/CD26.

Fletcher, Mary A, Zeng, Xiao R, Maher, Kevin et al.·PloS one·2010

This study tested whether two immune system markers could reliably identify ME/CFS patients. Researchers measured natural killer (NK) cell function—a type of immune cell that fights infections—and CD26, a protein found on immune cells. They found that ME/CFS patients had lower NK cell function and different patterns of CD26 compared to healthy people, suggesting these markers could potentially help diagnose the condition.

A formal analysis of cytokine networks in chronic fatigue syndrome.

Broderick, Gordon, Fuite, Jim, Kreitz, Andrea et al.·Brain, behavior, and immunity·2010

Researchers studied immune system chemicals called cytokines in people with ME/CFS and healthy controls to understand how their immune systems differ. Instead of looking at single markers, they examined how 16 different cytokines work together as networks. They found that people with ME/CFS have a very different immune system pattern—like a hub with one central point—compared to the more balanced network in healthy people.

Xenotropic murine leukemia virus-related gammaretrovirus in respiratory tract.

Fischer, Nicole, Schulz, Claudia, Stieler, Kristin et al.·Emerging infectious diseases·2010

Researchers looked for a virus called XMRV in respiratory samples (like saliva or mucus) from healthy and immunocompromised people. They found viral traces in a small percentage of healthy people (2-3%) and a higher percentage of immunocompromised people (10%). This study was one of several investigating whether XMRV might be linked to ME/CFS, though the findings were modest.

No evidence for XMRV in German CFS and MS patients with fatigue despite the ability of the virus to infect human blood cells in vitro.

Hohn, Oliver, Strohschein, Kristin, Brandt, Alexander U et al.·PloS one·2010

Researchers tested blood samples from German ME/CFS patients, multiple sclerosis patients with fatigue, and healthy people to see if a virus called XMRV was present. They looked for both antibodies (immune system markers) and viral genetic material. They found no evidence of XMRV in any of the groups, suggesting this virus is not associated with ME/CFS or MS-related fatigue in Germany.

Plasma IL-6, its soluble receptors and F2-isoprostanes at rest and during exercise in chronic fatigue syndrome.

Robinson, M, Gray, S R, Watson, M S et al.·Scandinavian journal of medicine & science in sports·2010

This study looked at specific markers of inflammation and oxidative stress (cellular damage) in people with ME/CFS compared to healthy individuals, both at rest and after exercise. Researchers found that a marker called F2-isoprostanes—which indicates oxidative stress—was consistently higher in ME/CFS patients. However, they did not find differences in inflammation markers like IL-6 between the two groups.

Anticardiolipin antibodies in the sera of patients with diagnosed chronic fatigue syndrome.

Hokama, Yoshitsugi, Campora, Cara Empey, Hara, Cynthia et al.·Journal of clinical laboratory analysis·2009

Researchers tested blood samples from ME/CFS patients and found abnormal antibodies called anticardiolipin antibodies (ACAs) in 95% of the samples. These antibodies mistakenly attack cardiolipin, a substance found in cell membranes. The study suggests that something in the immune system may be going wrong in ME/CFS, possibly affecting how cells produce energy.

RETRACTED: Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome.

Lombardi, Vincent C, Ruscetti, Francis W, Das Gupta, Jaydip et al.·Science (New York, N.Y.)·2009

This study, which has since been retracted, reported finding a virus called XMRV in blood cells from most ME/CFS patients tested, but rarely in healthy people. The researchers showed that this virus could be grown in the lab and transmitted between cells. However, subsequent studies by other scientists could not reproduce these findings, leading to the retraction of this paper.

Detection of herpesviruses and parvovirus B19 in gastric and intestinal mucosa of chronic fatigue syndrome patients.

Frémont, Marc, Metzger, Kristine, Rady, Hamada et al.·In vivo (Athens, Greece)·2009

Researchers looked for viral DNA from four viruses (HHV-6, HHV-7, EBV, and parvovirus B19) in the stomach and intestine samples from 48 ME/CFS patients and 35 healthy controls. They found that parvovirus B19 was much more common in patients with ME/CFS (40%) compared to healthy people (less than 15%), suggesting it may play a role in the illness for some patients. The other viruses were found at similar rates in both groups.

Plasma cytokines in women with chronic fatigue syndrome.

Fletcher, Mary Ann, Zeng, Xiao Rong, Barnes, Zachary et al.·Journal of translational medicine·2009

Researchers tested blood samples from women with ME/CFS and compared them to healthy women to look for immune system differences. They measured 16 different immune substances called cytokines and found that 10 of them were abnormal in ME/CFS patients—some were higher and some were lower than in healthy controls. While these differences suggest immune activation in ME/CFS, the pattern wasn't specific enough to use as a diagnostic test on its own.

An angiotensin-1 converting enzyme polymorphism is associated with allostatic load mediated by C-reactive protein, interleukin-6 and cortisol.

Smith, Alicia K, Maloney, Elizabeth M, Falkenberg, Virginia R et al.·Psychoneuroendocrinology·2009

This study looked at whether a specific genetic variation in a gene called ACE affects how people's bodies respond to stress and illness. Researchers measured multiple stress-related markers (inflammation, immune system activity, and cortisol levels) in people with and without ME/CFS. They found that people carrying a particular version of the ACE gene tended to have higher stress responses and more inflammation, suggesting genes may play a role in how severely someone's body reacts to stress.

Vitamin D metabolites as clinical markers in autoimmune and chronic disease.

Blaney, Greg P, Albert, Paul J, Proal, Amy D·Annals of the New York Academy of Sciences·2009

This study measured two types of vitamin D in the blood of patients with autoimmune and chronic diseases, including ME/CFS. The researchers found that a specific form of vitamin D (1,25-D) at high levels was associated with these conditions, but the commonly-tested form of vitamin D (25-D) was not. This suggests doctors may need to test for the right type of vitamin D to properly assess autoimmune disease.

Effect of supplement with lactic-acid producing bacteria on fatigue and physical activity in patients with chronic fatigue syndrome.

Sullivan, Asa, Nord, Carl E, Evengård, Birgitta·Nutrition journal·2009

This small study tested whether specific probiotic bacteria (live microorganisms that may benefit gut health) could reduce fatigue and improve physical activity in ME/CFS patients. Fifteen patients took probiotics for 4 weeks and were monitored for changes in fatigue, physical activity, and cognitive function. While some patients reported feeling better overall, the study did not find significant improvements in fatigue or activity levels, though cognitive function did improve.

Association of peripheral inflammatory markers with chronic fatigue in a population-based sample.

Raison, Charles L, Lin, Jin-Mann S, Reeves, William C·Brain, behavior, and immunity·2009

Researchers measured inflammation markers in the blood of people with ME/CFS, people with fatigue that didn't quite meet ME/CFS criteria, and healthy controls. They found that inflammation markers were elevated in both fatigue groups compared to healthy people. However, when they accounted for factors like depression, weight, age, and medications, the connection to ME/CFS specifically became less clear, suggesting that general fatigue and unwellness—not ME/CFS alone—may be linked to immune activation.

Autoantibodies, polymorphisms in the serotonin pathway, and human leukocyte antigen class II alleles in chronic fatigue syndrome: are they associated with age at onset and specific symptoms?

Ortega-Hernandez, Oscar-Danilo, Cuccia, Mariaclara, Bozzini, Sara et al.·Annals of the New York Academy of Sciences·2009

This study looked at whether certain genetic traits and immune markers in the blood are linked to when ME/CFS develops and what symptoms people experience. Researchers tested 81 ME/CFS patients for specific genes related to serotonin (a brain chemical), immune system genes, and antibodies. They found that different genetic patterns were associated with developing ME/CFS at different ages and with certain symptoms like joint pain and fever, but not muscle pain.

Molecular study of receptor for advanced glycation endproduct gene promoter and identification of specific HLA haplotypes possibly involved in chronic fatigue syndrome.

Carlo-Stella, N, Bozzini, S, De Silvestri, A et al.·International journal of immunopathology and pharmacology·2009

This study looked at two genes related to inflammation in 75 Italian ME/CFS patients and compared them to 141 healthy controls. The researchers found that certain genetic variations in the RAGE gene and immune system genes called HLA were more common in ME/CFS patients, suggesting these genetic differences might increase risk for the condition. The findings suggest ME/CFS may involve inherited factors that affect how the immune system responds.

Lower frequency of IL-17F sequence variant (His161Arg) in chronic fatigue syndrome patients.

Metzger, Kristine, Frémont, Marc, Roelant, Chris et al.·Biochemical and biophysical research communications·2008

This study looked at a genetic variation in a protein called IL-17F that affects immune system inflammation. Researchers found that ME/CFS patients were less likely to carry a protective version of this genetic variant compared to healthy people. This suggests that the immune system's inflammatory response, particularly from a type of immune cell called Th17 cells, may play a role in ME/CFS.

Glucocorticoid sensitivity of immune cells in severely fatigued adolescent girls: a longitudinal study.

ter Wolbeek, Maike, van Doornen, Lorenz J P, Schedlowski, Manfred et al.·Psychoneuroendocrinology·2008

This study looked at whether teenagers with severe fatigue have differences in how their immune cells respond to stress hormones called cortisol and dexamethasone. Researchers tracked 65 fatigued girls and 60 non-fatigued girls over a year, measuring their stress hormone levels and testing immune cell responses. They found that only girls whose fatigue persisted had reduced immune cell sensitivity to these stress hormones, suggesting that long-lasting fatigue may involve a specific change in how the immune system responds to stress.

Evidence for T-helper 2 shift and association with illness parameters in chronic fatigue syndrome (CFS).

Torres-Harding, Susan, Sorenson, Matthew, Jason, Leonard A et al.·Bulletin of the IACFS/ME·2008

This study looked at immune system differences in people with ME/CFS by measuring two types of immune cells called Th1 and Th2. Researchers found that people with ME/CFS who had a stronger shift toward Th2 immune responses also reported worse sleep quality and had higher stress hormone levels in their saliva. This suggests that immune system imbalances might be connected to some of the troubling symptoms people with ME/CFS experience.

Alterations in diurnal salivary cortisol rhythm in a population-based sample of cases with chronic fatigue syndrome.

Nater, Urs M, Youngblood, Laura Solomon, Jones, James F et al.·Psychosomatic medicine·2008

This study measured stress hormone (cortisol) levels and immune markers in saliva and blood from people with ME/CFS, people with significant fatigue who don't meet full CFS criteria, and healthy controls. People with ME/CFS showed an abnormal pattern: lower cortisol in the morning and higher in the evening (the opposite of what's healthy), suggesting their stress-response system may not be working normally.

A longitudinal study of the relationship between psychological distress and recurrence of upper respiratory tract infections in chronic fatigue syndrome.

Faulkner, Susan, Smith, Andrew·British journal of health psychology·2008

This study tracked 21 ME/CFS patients and 18 healthy people over 15 weeks to see if stress affects how often they catch colds and respiratory infections. ME/CFS patients caught infections much more frequently than healthy people, and importantly, high stress levels in one week predicted who would get sick the next week. The same stress also made their fatigue symptoms worse.

Low-grade inflammation and arterial wave reflection in patients with chronic fatigue syndrome.

Spence, Vance A, Kennedy, Gwen, Belch, Jill J F et al.·Clinical science (London, England : 1979)·2008

This study found that people with ME/CFS have stiffer arteries and higher levels of inflammation and oxidative stress (cellular damage) compared to healthy people. These cardiovascular changes are associated with each other and may increase the risk of future heart problems in people with ME/CFS.

Immunoassay with cytomegalovirus early antigens from gene products p52 and CM2 (UL44 and UL57) detects active infection in patients with chronic fatigue syndrome.

Beqaj, S H, Lerner, A M, Fitzgerald, J T·Journal of clinical pathology·2008

This study tested a new blood test method to detect active cytomegalovirus (CMV) infection in ME/CFS patients. The new test, called Copalis, was more sensitive than standard tests at finding signs of active CMV infection, detecting it in about 12% of CMV-exposed patients compared to only 2% with the older method. The researchers suggest this improved test could help identify a subset of ME/CFS patients who have active CMV infection.

Normalization of leaky gut in chronic fatigue syndrome (CFS) is accompanied by a clinical improvement: effects of age, duration of illness and the translocation of LPS from gram-negative bacteria.

Maes, Michael, Leunis, Jean-Claude·Neuro endocrinology letters·2008

This study tested whether taking natural anti-inflammatory supplements (glutamine, N-acetyl cysteine, and zinc) along with a special diet could help ME/CFS patients whose intestines had become too permeable ("leaky gut"). Researchers measured immune markers in the blood before and after 10-14 months of treatment and found that 24 out of 41 patients improved significantly, with the best results in younger patients and those with shorter illness duration.

Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut-intestinal permeability.

Maes, Michael, Mihaylova, Ivana, Leunis, Jean-Claude·Journal of affective disorders·2007

This study found that people with ME/CFS have higher levels of immune antibodies (IgA and IgM) that react against bacteria normally found in the gut. The researchers suggest this indicates the gut barrier may be more permeable (leaky), allowing bacterial products to enter the bloodstream and trigger an immune response. The study suggests testing for these antibodies might help identify and treat this potential gut problem in ME/CFS patients.

Defining the occurrence and influence of alpha-delta sleep in chronic fatigue syndrome.

Van Hoof, Elke, De Becker, Pascale, Lapp, Charles et al.·The American journal of the medical sciences·2007

This study looked at sleep patterns in 48 ME/CFS patients using overnight sleep recordings. Researchers found that patients had difficulty falling asleep, spent less time in deep restorative sleep, and showed an unusual pattern of brain waves (alpha-delta intrusion) during sleep. Interestingly, this abnormal sleep pattern was linked to anxiety rather than to immune system changes.

Reduced levels of oestrogen receptor beta mRNA in Swedish patients with chronic fatigue syndrome.

Gräns, Hanna, Nilsson, Maria, Dahlman-Wright, Karin et al.·Journal of clinical pathology·2007

This study looked at a protein called estrogen receptor beta in immune cells from ME/CFS patients and healthy people. Researchers found that ME/CFS patients had lower levels of this protein compared to healthy controls. Since estrogen plays a role in immune function and ME/CFS affects more women than men, this finding suggests hormone-related immune problems might be involved in the disease.

Not in the mind but in the cell: increased production of cyclo-oxygenase-2 and inducible NO synthase in chronic fatigue syndrome.

Maes, Michael, Mihaylova, Ivana, Kubera, Marta et al.·Neuro endocrinology letters·2007

This study found that people with ME/CFS have higher levels of two inflammatory molecules (COX-2 and iNOS) in their white blood cells compared to healthy people. The levels of these inflammatory markers were directly linked to how severe their symptoms were, including fatigue, pain, brain fog, and feeling like they have an infection. This suggests ME/CFS involves real inflammation in the body, not just psychological factors.

Not in the mind of neurasthenic lazybones but in the cell nucleus: patients with chronic fatigue syndrome have increased production of nuclear factor kappa beta.

Maes, Michael, Mihaylova, Ivana, Bosmans, Eugene·Neuro endocrinology letters·2007

This study found that people with ME/CFS have higher levels of a molecule called NF-kappa-beta in their white blood cells, both at rest and when stimulated by immune signals. This molecule controls inflammation and stress responses in cells. The higher the NF-kappa-beta levels, the more severe patients' symptoms—including fatigue, muscle pain, and feeling sick—were reported to be.

Longitudinal analysis of pro- and anti-inflammatory cytokine production in severely fatigued adolescents.

ter Wolbeek, Maike, van Doornen, Lorenz J P, Kavelaars, Annemieke et al.·Brain, behavior, and immunity·2007

This study compared immune system markers in severely fatigued teenagers, healthy teenagers, and a small group of ME/CFS patients over one year. While fatigued teenagers reported more depression, anxiety, and sleep problems similar to ME/CFS patients, their immune systems looked normal. Only the ME/CFS patients showed a distinct immune pattern with unusually high anti-inflammatory and low pro-inflammatory markers.

Hematologic and urinary excretion anomalies in patients with chronic fatigue syndrome.

Niblett, Suzanne H, King, Katrina E, Dunstan, R Hugh et al.·Experimental biology and medicine (Maywood, N.J.)·2007

Researchers compared blood and urine samples from 100 people with ME/CFS and 82 healthy controls to look for abnormalities. While standard blood tests appeared normal, closer examination found subtle differences in blood cell counts and patterns in how patients' bodies were processing and excreting amino acids (building blocks of protein) and other compounds in their urine.

Decreased expression of CD69 in chronic fatigue syndrome in relation to inflammatory markers: evidence for a severe disorder in the early activation of T lymphocytes and natural killer cells.

Mihaylova, Ivana, DeRuyter, Marcel, Rummens, Jean-Luc et al.·Neuro endocrinology letters·2007

This study looked at immune cell activation in people with ME/CFS by measuring a protein called CD69 on the surface of immune cells. Researchers found that ME/CFS patients had significantly lower levels of this activation marker on their T cells and natural killer cells compared to healthy people, even though the total number of immune cells was normal. This suggests that immune cells in ME/CFS may have trouble becoming activated properly in response to challenges.

Impaired natural immunity, cognitive dysfunction, and physical symptoms in patients with chronic fatigue syndrome: preliminary evidence for a subgroup?

Siegel, Scott D, Antoni, Michael H, Fletcher, Mary Ann et al.·Journal of psychosomatic research·2006

This study looked at whether a specific immune system measure called natural killer cell activity (NKCA) could help identify different subgroups of ME/CFS patients. Researchers compared 41 women with ME/CFS who had low NKCA levels to those with normal levels, measuring their cognitive ability and symptoms. They found that patients with low NKCA reported worse cognitive problems, more daytime dysfunction, and performed worse on thinking tests compared to those with normal NKCA levels.

Azithromycin in chronic fatigue syndrome (CFS), an analysis of clinical data.

Vermeulen, Ruud C W, Scholte, Hans R·Journal of translational medicine·2006

This study looked at whether azithromycin, an antibiotic with immune-modulating properties, could help ME/CFS patients. Researchers reviewed medical records from 99 patients who tried azithromycin after other treatments weren't sufficient. About 58 patients (roughly 59%) reported feeling better, and these responders had lower levels of a substance called acetylcarnitine in their blood.

Lower serum zinc in Chronic Fatigue Syndrome (CFS): relationships to immune dysfunctions and relevance for the oxidative stress status in CFS.

Maes, Michael, Mihaylova, Ivana, De Ruyter, Marcel·Journal of affective disorders·2006

This study found that people with ME/CFS have lower levels of zinc in their blood compared to healthy people. The lower the zinc level, the worse some symptoms were, especially feelings of infection. Zinc helps protect the body from harmful molecules called free radicals, so low zinc may be one reason why ME/CFS involves increased stress and damage in the body.

A first study of cytokine genomic polymorphisms in CFS: Positive association of TNF-857 and IFNgamma 874 rare alleles.

Carlo-Stella, N, Badulli, C, De Silvestri, A et al.·Clinical and experimental rheumatology·2006

This study looked at genetic variations in immune system genes among Italian ME/CFS patients to see if certain genetic patterns might make some people more prone to developing the condition. Researchers found that patients with ME/CFS were more likely to carry specific genetic variants in two genes (TNF and IFNgamma) that are involved in controlling inflammation. These findings suggest that genetic differences might influence how a person's immune system responds and could play a role in ME/CFS development.

Activation of human herpesviruses 6 and 7 in patients with chronic fatigue syndrome.

Chapenko, S, Krumina, A, Kozireva, S et al.·Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology·2006

This study looked at whether two common viruses (HHV-6 and HHV-7) that usually stay dormant in the body might be reactivating in people with ME/CFS. Researchers found that people with ME/CFS were more likely to have both viruses active at the same time, and when both were active, their immune cells showed signs of stress. This suggests these viruses might play a role in ME/CFS, though the study cannot prove they cause the disease.

Evaluation of autoantibodies to common and neuronal cell antigens in Chronic Fatigue Syndrome.

Vernon, Suzanne D, Reeves, William C·Journal of autoimmune diseases·2005

Researchers tested blood samples from people with ME/CFS and healthy controls to look for autoantibodies—proteins the immune system makes that can attack the body's own cells. They found that some people with ME/CFS had higher levels of antibodies against two specific targets: a brain protein called MAP2 and a component of DNA. However, most common autoantibodies were not elevated in ME/CFS patients.

Exercise capacity and immune function in male and female patients with chronic fatigue syndrome (CFS).

Snell, Christopher R, Vanness, J Mark, Strayer, David R et al.·In vivo (Athens, Greece)·2005

This study looked at whether a specific immune system problem affects how much exercise people with ME/CFS can do. Researchers tested 106 ME/CFS patients (35 men and 71 women) on exercise machines and found that patients with abnormal immune activity had noticeably lower exercise capacity than those with normal immune function. The difference was about the same for both men and women.

Lymphocyte subset differences in patients with chronic fatigue syndrome, multiple sclerosis and major depression.

Robertson, M J, Schacterle, R S, Mackin, G A et al.·Clinical and experimental immunology·2005

This study looked at immune cells in the blood of people with ME/CFS and compared them to people with depression, multiple sclerosis, and healthy individuals. While the total numbers of major immune cell types were similar across groups, researchers found differences in specific subtypes of these cells, particularly in natural killer cells. This suggests that ME/CFS may involve changes in how the immune system is organized, even if total cell counts appear normal.

Spinal fluid abnormalities in patients with chronic fatigue syndrome.

Natelson, Benjamin H, Weaver, Shelley A, Tseng, Chin-Lin et al.·Clinical and diagnostic laboratory immunology·2005

Researchers performed spinal taps on 44 ME/CFS patients and 13 healthy people to look for signs of brain inflammation. They found that 30% of ME/CFS patients had abnormal levels of white blood cells or proteins in their spinal fluid, compared to none in the healthy group. They also found that certain immune molecules were different in ME/CFS patients, particularly in those with sudden flu-like symptom onset. These results suggest that ME/CFS may involve real physical changes in the nervous system, not just psychological factors.

Chronic fatigue syndrome: exercise performance related to immune dysfunction.

Nijs, Jo, Meeus, Mira, McGregor, Neil R et al.·Medicine and science in sports and exercise·2005

This study looked at whether problems with the immune system might explain why people with ME/CFS feel exhausted after exercise and cannot exercise as much as healthy people. Researchers tested 16 ME/CFS patients' immune cells and had them exercise on a stationary bike while measuring their oxygen use and heart rate. They found that two specific immune markers—elastase and protein kinase R—were linked to reduced exercise capacity, suggesting immune dysfunction may play a role in abnormal exercise responses.

Stress-induced changes in LPS-induced pro-inflammatory cytokine production in chronic fatigue syndrome.

Gaab, Jens, Rohleder, Nicolas, Heitz, Vera et al.·Psychoneuroendocrinology·2005

This study tested how ME/CFS patients' immune systems respond to stress compared to healthy people. Researchers gave both groups a stressful public speaking task, then exposed their blood samples to a bacterial substance to measure immune response. Unlike healthy controls whose immune response increased after stress, ME/CFS patients showed a decreased immune response, suggesting their bodies may not mobilize infection-fighting chemicals normally during stress.

Decreased dehydroepiandrosterone sulfate but normal insulin-like growth factor in chronic fatigue syndrome (CFS): relevance for the inflammatory response in CFS.

Maes, Michael, Mihaylova, Ivana, De Ruyter, Marcel·Neuro endocrinology letters·2005

This study compared hormone levels in people with ME/CFS to healthy controls. Researchers found that ME/CFS patients had significantly lower levels of DHEAS (a hormone made by the adrenal glands), but normal levels of another hormone called IGF1. The low DHEAS was closely linked to markers of immune system activation and inflammation, suggesting this hormone imbalance may contribute to ME/CFS symptoms.

[Prevalence of atopy in chronic fatigue syndrome].

Ferré Ybarz, L, Cardona Dahl, V, Cadahía García, A et al.·Allergologia et immunopathologia·2005

Researchers compared allergies and allergic sensitivity in 25 people with ME/CFS to 20 healthy controls. While patients with ME/CFS reported slightly more respiratory symptoms and drug allergies, the study found no significant difference in overall allergic sensitization between the two groups. This suggests that allergies may not be a core feature of ME/CFS, though some patients do experience them.

Association of chronic fatigue syndrome with human leucocyte antigen class II alleles.

Smith, J, Fritz, E L, Kerr, J R et al.·Journal of clinical pathology·2005

This study looked at whether certain genetic markers related to the immune system (called HLA types) are more common in people with ME/CFS than in healthy people. Researchers compared the genetic profiles of 49 ME/CFS patients with 102 healthy controls from the same region of England. They found that one particular genetic marker (HLA-DQA1*01) was significantly more common in ME/CFS patients, suggesting genes may play a role in who develops this illness.

Increased neutrophil apoptosis in chronic fatigue syndrome.

Kennedy, G, Spence, V, Underwood, C et al.·Journal of clinical pathology·2004

This study found that people with ME/CFS have more dying white blood cells (neutrophils) and fewer healthy ones compared to people without the condition. The researchers also discovered that ME/CFS patients have higher levels of a chemical called TGF-beta1 that can trigger cell death. These findings suggest that ME/CFS involves measurable problems with the immune system that can be detected in a blood test.

Study of immune alterations in patients with chronic fatigue syndrome with different etiologies.

Racciatti, D, Dalessandro, M, Delle Donne, L et al.·International journal of immunopathology and pharmacology·2004

This study looked at immune system cells in people with ME/CFS to see if there were differences compared to healthy people. Researchers tested blood samples from 139 ME/CFS patients and 36 healthy controls, examining specific types of white blood cells. They found that people with ME/CFS had lower counts of certain immune cells, suggesting the immune system may play a role in causing or maintaining the condition.

IgM serum antibodies to Epstein-Barr virus are uniquely present in a subset of patients with the chronic fatigue syndrome.

Lerner, A Martin, Beqaj, Safedin H, Deeter, Robert G et al.·In vivo (Athens, Greece)·2004

Researchers tested blood samples from 58 ME/CFS patients and 68 healthy controls for antibodies to Epstein-Barr virus (EBV), a common virus that causes mononucleosis. They found that about half of the ME/CFS patients (33 out of 58) had elevated levels of a specific type of antibody called IgM against EBV, while none of the healthy controls had this pattern. These antibody levels stayed elevated in ME/CFS patients for up to 3.5 years, suggesting this test might help identify a particular subgroup of ME/CFS patients.

Enhanced glucocorticoid sensitivity in patients with chronic fatigue syndrome.

Gaab, Jens, Rohleder, Nicolas, Heitz, Vera et al.·Acta neuropsychiatrica·2003

This study looked at how the bodies of ME/CFS patients respond to stress hormones called glucocorticoids (particularly cortisol). Researchers gave 21 ME/CFS patients and 20 healthy people a stressful social task, then measured their cortisol levels and how sensitive their immune cells were to glucocorticoids. They found that ME/CFS patients' immune cells were more sensitive to these stress hormones than healthy people's cells, even though their cortisol levels rose similarly to controls.

Complement activation in a model of chronic fatigue syndrome.

Sorensen, Bristol, Streib, Joanne E, Strand, Matthew et al.·The Journal of allergy and clinical immunology·2003

Researchers asked people with ME/CFS and healthy controls to exercise on a stationary bike, then tracked their symptoms and blood markers over the following week. They found that people with ME/CFS had a specific increase in a immune system marker called C4a six hours after exercise, and their fatigue and reduced activity worsened significantly, while healthy controls did not show these changes.

Predictive immunophenotypes: disease-related profile in chronic fatigue syndrome.

Stewart, Carleton C, Cookfair, Diane L, Hovey, Kathleen M et al.·Cytometry. Part B, Clinical cytometry·2003

This study compared immune system cells called natural killer (NK) cells and cytotoxic T cells between people with ME/CFS and healthy controls. Researchers found that people with ME/CFS had different patterns of these immune cells compared to healthy people, but interestingly, healthy people living in the same town as ME/CFS cases had immune cell patterns that looked more similar to ME/CFS patients. This suggests that living in an area where ME/CFS is common might affect how people's immune systems work.

Diagnostic evaluation of 2', 5'-oligoadenylate synthetase activities and antibodies against Epstein-Barr virus and Coxiella burnetii in patients with chronic fatigue syndrome in Japan.

Ikuta, Kazufumi, Yamada, Takeshi, Shimomura, Tokio et al.·Microbes and infection·2003

This study tested whether certain viral infections and immune system markers are linked to ME/CFS. Researchers measured a protein called 2-5AS in blood cells from ME/CFS patients in Japan and compared it to healthy people. They found that ME/CFS patients had higher levels of this immune marker than healthy controls, and some patients showed signs of past infections with Epstein-Barr virus or another bacteria.

Multiple co-infections (Mycoplasma, Chlamydia, human herpes virus-6) in blood of chronic fatigue syndrome patients: association with signs and symptoms.

Nicolson, G L, Gan, R, Haier, J·APMIS : acta pathologica, microbiologica, et immunologica Scandinavica·2003

This study tested the blood of 200 ME/CFS patients and 100 healthy controls for three types of infections: Mycoplasma bacteria, Chlamydia bacteria, and human herpesvirus-6 (HHV-6). The researchers found that ME/CFS patients had significantly higher rates of these infections compared to healthy people, and patients with multiple infections at the same time tended to have more severe symptoms.

RNase L levels in peripheral blood mononuclear cells: 37-kilodalton/83-kilodalton isoform ratio is a potential test for chronic fatigue syndrome.

Tiev, Kiet Phong, Demettre, Edith, Ercolano, Philippe et al.·Clinical and diagnostic laboratory immunology·2003

This study looked at a protein called RNase L in the immune cells of ME/CFS patients and healthy people. Researchers found that ME/CFS patients had a different pattern of RNase L forms compared to healthy volunteers, and this pattern could potentially be used as a simple blood test to help diagnose ME/CFS. The test showed promise in distinguishing ME/CFS patients from healthy people in this small group.

Associations between bronchial hyperresponsiveness and immune cell parameters in patients with chronic fatigue syndrome.

Nijs, Jo, De Becker, Pascale, De Meirleir, Kenny et al.·Chest·2003

Some ME/CFS patients experience unusual airway sensitivity (called bronchial hyperresponsiveness), but the reason why is unclear. This study tested whether this airway sensitivity is caused by specific immune system problems. Researchers found that patients with airway sensitivity had different immune cell patterns than healthy people, but these differences were not the same type seen in asthma, suggesting a different mechanism is at work.

Normal production of inflammatory cytokines in chronic fatigue and fibromyalgia syndromes determined by intracellular cytokine staining in short-term cultured blood mononuclear cells.

Amel Kashipaz, M R, Swinden, D, Todd, I et al.·Clinical and experimental immunology·2003

Researchers tested whether immune system cells from ME/CFS and fibromyalgia patients produce abnormal levels of inflammatory chemicals called cytokines. Using advanced microscopy techniques to examine individual immune cells, they found that cytokine production was normal in patients compared to healthy controls. This suggests that abnormal cytokine production may not be the main cause of these conditions.

Autoantibodies against muscarinic cholinergic receptor in chronic fatigue syndrome.

Tanaka, Susumu, Kuratsune, Hirohiko, Hidaka, Yoh et al.·International journal of molecular medicine·2003

This study found that about half of ME/CFS patients have unusual antibodies (immune proteins) that target a specific brain receptor involved in muscle control and nervous system function. Patients with these antibodies reported more muscle weakness and cognitive problems than those without them. This suggests that in some ME/CFS patients, the immune system may be mistakenly attacking the body's own nerve receptors.

Cellular immunity in monozygotic twins discordant for chronic fatigue syndrome.

Sabath, Daniel E, Barcy, Serge, Koelle, David M et al.·The Journal of infectious diseases·2002

This study looked at immune system differences in identical twins where one twin had ME/CFS and the other didn't. By comparing identical twins, researchers could focus on immune changes related to the illness rather than genetic differences. The study found that certain immune cells were more variable in twins with ME/CFS, suggesting the immune system may be less stable in this condition.

Utility of the blood for gene expression profiling and biomarker discovery in chronic fatigue syndrome.

Vernon, Suzanne D, Unger, Elizabeth R, Dimulescu, Irina M et al.·Disease markers·2002

Researchers examined blood cells from people with ME/CFS and healthy volunteers to see if they could find differences in how genes are turned on or off. They found that blood cells from ME/CFS patients showed different gene activity patterns compared to healthy people, and some of these differences involved immune system genes. This suggests that ME/CFS involves problems with how the immune system is functioning.

Physical performance and prediction of 2-5A synthetase/RNase L antiviral pathway activity in patients with chronic fatigue syndrome.

Snell, Christopher R, Vanness, J Mark, Strayer, David R et al.·In vivo (Athens, Greece)·2002

This study looked at whether exercise test results could predict high levels of RNase L, an enzyme that may be involved in ME/CFS. Researchers asked 73 patients to exercise until they were exhausted, and found that those with elevated RNase L had lower exercise capacity than those with normal levels. The findings suggest that simple exercise tests might help doctors identify which ME/CFS patients have this particular biological abnormality.

IgM serum antibodies to human cytomegalovirus nonstructural gene products p52 and CM2(UL44 and UL57) are uniquely present in a subset of patients with chronic fatigue syndrome.

Lerner, A Martin, Beqaj, Safedin H, Deeter, Robert G et al.·In vivo (Athens, Greece)·2002

Researchers tested blood samples from ME/CFS patients and healthy controls for specific antibodies to cytomegalovirus (CMV), a common virus. They found that 16 ME/CFS patients had unique antibodies to two CMV proteins (p52 and CM2) that were not found in 77 control subjects, including other ME/CFS patients and healthy people. This suggests these antibodies might be a specific marker for a subset of ME/CFS patients and could indicate an ongoing or incomplete CMV infection in this group.

Prevalence of allergen-specific IgE among patients with chronic fatigue syndrome.

Kowal, Krzysztof, Schacterele, Richard S, Schur, Peter H et al.·Allergy and asthma proceedings·2002

This study tested 50 ME/CFS patients for allergies by measuring specific immune proteins called allergen-specific IgE in their blood. Contrary to earlier patient surveys suggesting very high allergy rates, only 36% of ME/CFS patients had detectable allergic antibodies to common allergens like dust mites, pollen, and foods. This rate was similar to what researchers find in the general healthy population, suggesting that allergies may not be uniquely associated with ME/CFS.

Cytokines in nasal lavage fluids from acute sinusitis, allergic rhinitis, and chronic fatigue syndrome subjects.

Repka-Ramirez, Susana, Naranch, Kristina, Park, Yong-Jin et al.·Allergy and asthma proceedings·2002

Researchers measured inflammation markers in nasal fluid samples from people with ME/CFS, allergic rhinitis, acute sinusitis, and healthy controls. They found that people with acute sinusitis had significantly higher levels of inflammatory substances, but people with ME/CFS did not show elevated inflammation in their nasal passages compared to healthy controls.

Influenza vaccination: is it appropriate in chronic fatigue syndrome?

Sleigh, Kenna M, Marra, Fawziah H, Stiver, H Grant·American journal of respiratory medicine : drugs, devices, and other interventions·2002

This study looked at whether people with ME/CFS should get the flu vaccine, since many patients worry it might worsen their symptoms or harm their already-altered immune system. Researchers reviewed patient concerns and clinical trial data and found that flu vaccination actually produces protective antibodies in ME/CFS patients without making their symptoms worse, though some patients reported more side effects after the shot (which turned out to overlap with ME/CFS symptoms they already had).

Immunological variables mediate cognitive dysfunction in gulf war veterans but not civilians with chronic fatigue syndrome.

Brimacombe, Michael, Zhang, QuanWu, Lange, Gudrun et al.·Neuroimmunomodulation·2002

This study compared immune system markers and thinking/memory problems in Gulf War veterans with ME/CFS and civilians with ME/CFS. The researchers found that in Gulf War veterans, certain immune system patterns were connected to cognitive problems like slower reaction times, and these immune changes seemed to affect how well they could function. Interestingly, this same immune-cognition relationship was not found in civilians with ME/CFS, suggesting the two groups may have different underlying causes for their illness.

Antiviral pathway activation in patients with chronic fatigue syndrome and acute infection.

Gow, J W, Simpson, K, Behan, P O et al.·Clinical infectious diseases : an official publication of the Infectious Diseases Society of America·2001

Researchers compared two immune system defense pathways (RNase L and PKR) in people with ME/CFS, people with acute stomach infections, and healthy people. The immune pathways were only activated in people with acute infections, not in people with ME/CFS or healthy controls. This finding suggests that these particular immune markers cannot be used as a simple diagnostic test for ME/CFS.

Lack of association between HLA genotype and chronic fatigue syndrome.

Underhill, J A, Mahalingam, M, Peakman, M et al.·European journal of immunogenetics : official journal of the British Society for Histocompatibility and Immunogenetics·2001

Researchers tested whether certain immune system genes (HLA genes) were more common in ME/CFS patients compared to healthy people. They studied 58 ME/CFS patients and 134 healthy controls using modern genetic testing methods. They found no significant differences in HLA genes between the two groups, suggesting that these particular immune genes are not a major cause of ME/CFS.

IgE levels are the same in chronic fatigue syndrome (CFS) and control subjects when stratified by allergy skin test results and rhinitis types.

Repka-Ramirez, M S, Naranch, K, Park, Y J et al.·Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology·2001

Researchers tested whether people with ME/CFS have higher levels of IgE, a protein the immune system makes during allergic reactions. They compared IgE levels in 95 ME/CFS patients and 109 healthy people, including those with and without allergies. They found IgE levels were the same in both groups, suggesting that allergies are probably not a major cause of ME/CFS.

A biochemical analysis of people with chronic fatigue who have Irlen Syndrome: speculation concerning immune system dysfunction.

Robinson, G L, McGregor, N R, Roberts, T K et al.·Perceptual and motor skills·2001

This study looked at 61 people with ME/CFS to see if they also had a visual processing problem called Irlen Syndrome (where certain patterns and lighting cause visual discomfort). Researchers found that people with more severe visual problems had different levels of certain fats and amino acids in their blood and urine compared to those with milder visual symptoms. The authors suggest these differences might show signs of immune system activation, possibly from an infection.

Salivary gland changes in chronic fatigue syndrome: a case-controlled preliminary histologic study.

Woo, S B, Schacterle, R S, Komaroff, A L et al.·Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics·2000

Researchers examined tiny salivary glands in the lips of 11 ME/CFS patients and compared them to healthy controls. They found that ME/CFS patients had various changes in these glands, including swelling, scarring, and immune cell infiltration. Most notably, ME/CFS patients had significantly more mast cells (immune cells) in their salivary glands than controls, suggesting these glands may be damaged in ME/CFS.

Frequent HHV-6 reactivation in multiple sclerosis (MS) and chronic fatigue syndrome (CFS) patients.

Ablashi, D V, Eastman, H B, Owen, C B et al.·Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology·2000

This study looked at whether a common virus called HHV-6 might be reactivated in ME/CFS patients. Researchers found that ME/CFS and MS patients had higher levels of antibodies (immune markers) to HHV-6 compared to healthy people, and they detected active virus in blood cells from these patients. The findings suggest that HHV-6 reactivation might play a role in causing or worsening ME/CFS symptoms.

A 37 kDa 2-5A binding protein as a potential biochemical marker for chronic fatigue syndrome.

De Meirleir, K, Bisbal, C, Campine, I et al.·The American journal of medicine·2000

Researchers found a specific protein (37 kDa) in the blood cells of 88% of ME/CFS patients, compared to only 28% of control subjects. This protein was present in much higher amounts in ME/CFS patients, suggesting it could potentially be used as a blood test to help identify the condition.

Chronic fatigue syndrome and nickel allergy.

Marcusson, J A, Lindh, G, Evengård, B·Contact dermatitis·1999

This study tested 50 patients with ME/CFS and 73 healthy people for allergic reactions to eight different metals. Researchers found that people with ME/CFS were more likely to be allergic to nickel—36% of ME/CFS patients had nickel allergies compared to only 19% of healthy people. This difference was especially pronounced in women with ME/CFS, where over half (52%) showed nickel allergy. The researchers suggest that nickel exposure might somehow trigger or contribute to ME/CFS in some people.

TNF-alpha and chronic fatigue syndrome.

Moss, R B, Mercandetti, A, Vojdani, A·Journal of clinical immunology·1999

This study looked at whether a molecule called TNF-alpha, which helps control inflammation in the body, is elevated in people with ME/CFS. Researchers compared blood levels of TNF-alpha in patients with ME/CFS to healthy people without the condition. They found that people with ME/CFS had significantly higher levels of TNF-alpha, suggesting that inflammation may play a role in the disease.

Changes in immune parameters seen in Gulf War veterans but not in civilians with chronic fatigue syndrome.

Zhang, Q, Zhou, X D, Denny, T et al.·Clinical and diagnostic laboratory immunology·1999

This study compared immune system markers in people with ME/CFS, looking separately at Gulf War veterans and non-veterans. Researchers found that Gulf War veterans with ME/CFS had different immune patterns (more of certain types of T cells, fewer NK cells, and higher levels of inflammation markers) compared to healthy veterans. However, non-veterans with ME/CFS showed no such immune differences from healthy controls, suggesting Gulf War service may have affected the immune system differently than sporadic ME/CFS.

Human herpesviruses in chronic fatigue syndrome.

Wallace, H L, Natelson, B, Gause, W et al.·Clinical and diagnostic laboratory immunology·1999

Researchers tested whether common viruses (HHV6, HHV7, Epstein-Barr virus, and cytomegalovirus) are more active or present in people with ME/CFS compared to healthy people. They examined blood samples from ME/CFS patients and matched healthy controls, looking for both the viruses themselves and antibodies (immune markers) against these viruses. They found no significant differences between the two groups, suggesting these particular viruses may not be a primary driver of ME/CFS.

Mercury and nickel allergy: risk factors in fatigue and autoimmunity.

Sterzl, Ivan, Procházková, Jarmila, Hrdá, Pavlína et al.·Neuro endocrinology letters·1999

This study tested whether allergies to metals like mercury (found in old dental fillings) and nickel might trigger fatigue and autoimmune problems in people with ME/CFS. Researchers compared three groups of tired patients with healthy controls and found that people with fatigue were more sensitive to these metals. When some patients had their mercury-containing fillings removed and replaced, their fatigue improved significantly.

Metal-specific lymphocytes: biomarkers of sensitivity in man.

Stejskal, Vera DM, Danersund, Antero, Lindvall, Anders et al.·Neuro endocrinology letters·1999

This study tested whether people with ME/CFS-like symptoms had immune reactions to metals in their dental fillings and other restorations. Researchers found that many patients had immune cells that reacted to metals like mercury, nickel, and gold, and that 76% of patients who replaced their metal restorations with non-metal alternatives reported feeling better. The study suggests that metal sensitivity might trigger inflammatory responses that contribute to chronic fatigue and related conditions.

Yersinia enterocolitica and the chronic fatigue syndrome.

Swanink, C M, Stolk-Engelaar, V M, van der Meer, J W et al.·The Journal of infection·1998

This study looked for signs that a bacterium called Yersinia enterocolitica might cause ME/CFS by testing blood samples from 88 ME/CFS patients and 77 healthy people. Researchers found that antibodies (immune markers) to this bacterium were equally common in both groups, suggesting this particular infection is unlikely to be a major cause of ME/CFS.

Rhinitis symptoms in chronic fatigue syndrome.

Baraniuk, J N, Clauw, D J, Gaumond, E·Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology·1998

This study looked at whether people with ME/CFS have more nasal and sinus problems than the general population. Researchers compared 51 ME/CFS patients with healthy controls and people with allergies, using questionnaires and allergy skin tests. They found that most ME/CFS patients reported significant nasal and sinus symptoms, but about half of these cases appeared to be non-allergic in nature.

Chronic fatigue syndrome: identification of distinct subgroups on the basis of allergy and psychologic variables.

Borish, L, Schmaling, K, DiClementi, J D et al.·The Journal of allergy and clinical immunology·1998

This study looked at whether allergies and psychological factors play a role in ME/CFS. Researchers compared 18 people with ME/CFS to healthy controls, people with allergies, and people with depression. They found that people with ME/CFS had different immune molecules (called cytokines) in their blood compared to healthy people, similar to those with allergies. Interestingly, people with ME/CFS who also had certain psychological profiles showed different immune patterns, suggesting that both allergies and how the mind responds to them may contribute to ME/CFS in some patients.

A study of the immunology of the chronic fatigue syndrome: correlation of immunologic parameters to health dysfunction.

Hassan, I S, Bannister, B A, Akbar, A et al.·Clinical immunology and immunopathology·1998

This study examined immune system markers in 44 people with ME/CFS to see how these markers related to symptom severity and mental health. Researchers found that ME/CFS patients had unusual patterns in their immune cells—specifically, signs of increased immune activation and changes in how lymphocytes (white blood cells) behave. These immune changes correlated with worse physical function, pain, and mental health symptoms.

Immunologic parameters in chronic fatigue syndrome, major depression, and multiple sclerosis.

Natelson, B H, LaManca, J J, Denny, T N et al.·The American journal of medicine·1998

Researchers compared blood immune system markers between ME/CFS patients, people with depression, people with multiple sclerosis, and healthy controls. They measured 18 different immune system measurements, looking for signs that ME/CFS involves immune system problems. The study found only minor differences in one immune protein between ME/CFS patients and healthy controls, and these differences disappeared when comparing across all three disease groups.

Detection of Mycoplasma genus and Mycoplasma fermentans by PCR in patients with Chronic Fatigue Syndrome.

Vojdani, A, Choppa, P C, Tagle, C et al.·FEMS immunology and medical microbiology·1998

Researchers tested blood samples from 100 ME/CFS patients and 50 healthy people to see if a bacterium called Mycoplasma fermentans was present. They found this bacterium's genetic material in more than a third of ME/CFS patients compared to only 8% of healthy controls. Patients with higher amounts of the bacterium also had stronger immune responses against it, suggesting their bodies were reacting to the infection.

Reproductive correlates of chronic fatigue syndrome.

Harlow, B L, Signorello, L B, Hall, J E et al.·The American journal of medicine·1998

This study compared reproductive and menstrual histories in women with ME/CFS to healthy women without the condition. Women with ME/CFS reported more gynecologic problems and irregular menstrual cycles, and researchers found signs suggesting ovarian dysfunction—such as polycystic ovary syndrome (PCOS)—occurred more often in the ME/CFS group. The authors propose that hormonal imbalances affecting egg release may contribute to ME/CFS by reducing protective immune effects from certain hormones.

Nasal secretion analysis in allergic rhinitis, cystic fibrosis, and nonallergic fibromyalgia/chronic fatigue syndrome subjects.

Baraniuk, J N, Clauw, D, Yuta, A et al.·American journal of rhinology·1998

Many people with ME/CFS experience nasal congestion and rhinitis symptoms, but don't test positive for allergies. This study analyzed nasal fluid from ME/CFS patients and compared it to people with allergies, cystic fibrosis, and healthy controls to understand what might be causing these symptoms. The researchers found that ME/CFS patients' nasal fluid looked similar to healthy controls, suggesting that the constant baseline secretion processes in the nose are not abnormal in ME/CFS.

Chronic fatigue syndrome.

Mawle, A C·Immunological investigations·1997

This study examined whether ME/CFS might be caused by an infection or involve immune system problems. While researchers didn't find a specific virus or bacteria responsible for the illness, they discovered that when they grouped patients based on whether their symptoms started suddenly or gradually, some differences in immune markers appeared between patients and healthy people.

Electron microscopic immunocytological profiles in chronic fatigue syndrome.

Holmes, M J, Diack, D S, Easingwood, R A et al.·Journal of psychiatric research·1997

Researchers used a special microscope to examine immune cells from ME/CFS patients and found structures that resembled a type of virus in 10 out of 17 patients, but not in healthy control subjects. However, when they tried to confirm this finding using additional testing methods, the results were unclear. This suggests something might be different in the cells of some ME/CFS patients, but more research is needed to understand what it means.

[Demonstration on Borna disease virus in patients with chronic fatigue syndrome].

Nakaya, T, Kuratsune, H, Kitani, T et al.·Nihon rinsho. Japanese journal of clinical medicine·1997

Researchers tested whether a virus called Borna disease virus (BDV) might be connected to ME/CFS. They found that some patients with ME/CFS had signs of BDV infection, and the virus was also detected in one family where multiple members had ME/CFS. While these findings suggest BDV could play a role, the study shows it's likely not the sole cause of ME/CFS.

Immune responses associated with chronic fatigue syndrome: a case-control study.

Mawle, A C, Nisenbaum, R, Dobbins, J G et al.·The Journal of infectious diseases·1997

Researchers compared immune system measurements between ME/CFS patients and healthy controls to see if immune differences could reliably detect the illness. While previous studies reported many immune differences, this careful study found most standard immune tests showed no difference between patients and controls. However, when they looked at specific subgroups—such as patients whose illness started suddenly versus gradually—they did find some immune differences, suggesting that ME/CFS may not be a single uniform immune condition.

Elevation of bioactive transforming growth factor-beta in serum from patients with chronic fatigue syndrome.

Bennett, A L, Chao, C C, Hu, S et al.·Journal of clinical immunology·1997

Researchers measured a protein called TGF-beta in the blood of ME/CFS patients and compared it to healthy people and patients with other diseases like lupus and multiple sclerosis. They found that ME/CFS patients had significantly higher levels of this protein than all the other groups studied. This suggests that TGF-beta might play a role in ME/CFS, though more research is needed to understand exactly how.

Markers of inflammation and immune activation in chronic fatigue and chronic fatigue syndrome.

Buchwald, D, Wener, M H, Pearlman, T et al.·The Journal of rheumatology·1997

Researchers tested blood samples from 153 patients with severe fatigue to see if certain immune markers were elevated, thinking that an overactive immune system might cause ME/CFS. They found that three markers (C-reactive protein, beta 2-microglobulin, and neopterin) were higher in fatigued patients compared to healthy controls, but these markers couldn't reliably distinguish between ME/CFS and other types of chronic fatigue. The results suggest that some patients have signs of immune activation, but it's unclear whether this is a temporary response to infection or part of the ongoing illness.

[High prevalence without reactivation of herpes virus 6 in subjects with chronic fatigue syndrome].

Cuende, J I, Civeira, P, Diez, N et al.·Anales de medicina interna (Madrid, Spain : 1984)·1997

Researchers tested 20 ME/CFS patients for active herpesvirus-6 (HHV-6) infection, a virus that had been suspected as a possible cause of ME/CFS. They found that half the patients had antibodies showing past HHV-6 infection, but sensitive testing detected only small amounts of viral DNA in blood cells and no active viral replication. This suggests that while many ME/CFS patients may have been infected with HHV-6 in the past, the virus is not actively multiplying in their bodies.

High frequency of autoantibodies to insoluble cellular antigens in patients with chronic fatigue syndrome.

von Mikecz, A, Konstantinov, K, Buchwald, D S et al.·Arthritis and rheumatism·1997

Researchers tested blood samples from 60 ME/CFS patients and found that 83% had unusual antibodies (immune proteins) attacking their own cells—specifically targeting proteins that form the structural framework inside and around cell nuclei. These antibodies were rarely seen in healthy people (only 17%), suggesting this autoimmune pattern might be unique to ME/CFS and could potentially help doctors identify the disease.

Possible correlation between Borna disease virus infection and Japanese patients with chronic fatigue syndrome.

Kitani, T, Kuratsune, H, Fuke, I et al.·Microbiology and immunology·1996

This 1996 study investigated whether a virus called Borna disease virus (BDV) might be connected to chronic fatigue syndrome (ME/CFS). Borna disease virus naturally infects animals like horses and sheep, and researchers found evidence of this virus or antibodies to it in some ME/CFS patients. The study suggests there may be a link between BDV infection and ME/CFS symptoms, though more research is needed to understand if and how this virus contributes to the condition.

Lymphocyte subsets, apoptosis, and cytokines in patients with chronic fatigue syndrome.

Swanink, C M, Vercoulen, J H, Galama, J M et al.·The Journal of infectious diseases·1996

This study compared immune system markers in blood samples from 76 ME/CFS patients and 69 healthy controls to see if immune abnormalities could explain fatigue severity. Researchers found one immune marker (CD11b on CD8 cells) was lower in ME/CFS patients, but most other immune measures were similar between groups, and none of these markers correlated with how severe a patient's fatigue or depression was.

No findings of enteroviruses in Swedish patients with chronic fatigue syndrome.

Lindh, G, Samuelson, A, Hedlund, K O et al.·Scandinavian journal of infectious diseases·1996

Researchers tested 34 Swedish patients with ME/CFS to see if a virus called enterovirus might be causing their illness. They looked for the virus in stool samples, blood, spinal fluid, and muscle tissue using several different detection methods. The study found no evidence of enterovirus infection in any of the patients tested.

The influence of age on transfer factor treatment of cellular immunodeficiency, chronic fatigue syndrome and/or chronic viral infections.

Hana, I, Vrubel, J, Pekarek, J et al.·Biotherapy (Dordrecht, Netherlands)·1996

This study looked at 222 patients with weak immune systems, many of whom also had ME/CFS and/or chronic viral infections (EBV or CMV). They were treated with transfer factor, a type of immune-boosting therapy, given as injections over 8 weeks. The researchers found that younger patients improved more often than older patients, with failure rates rising significantly in those over 54 years old.

Viral serologies in patients with chronic fatigue and chronic fatigue syndrome.

Buchwald, D, Ashley, R L, Pearlman, T et al.·Journal of medical virology·1996

Researchers tested 548 people with chronic fatigue to see if they had unusually high levels of antibodies to 13 common viruses, since ME/CFS often starts suddenly after a viral illness. They compared antibody levels in patients with chronic fatigue to healthy controls and found no consistent differences between the groups, suggesting these particular virus tests are not helpful in diagnosing or understanding chronic fatigue.

The value of the dehydroepiandrosterone-annexed vitamin C infusion treatment in the clinical control of chronic fatigue syndrome (CFS). II. Characterization of CFS patients with special reference to their response to a new vitamin C infusion treatment.

Kodama, M, Kodama, T, Murakami, M·In vivo (Athens, Greece)·1996

This 1996 study examined whether high-dose vitamin C infusions, with or without a hormone called DHEA added, could help treat ME/CFS. Researchers treated 313 patients with chronic pneumonia-like illness that matched ME/CFS symptoms, often combined with antibiotics. The authors found that the combination of two types of vitamin C infusions worked better than one type alone, suggesting that low levels of certain body hormones might play a role in ME/CFS.

Eosinophil cationic protein serum levels and allergy in chronic fatigue syndrome.

Conti, F, Magrini, L, Priori, R et al.·Allergy·1996

This study measured a protein called eosinophil cationic protein (ECP) in the blood of ME/CFS patients to see if their immune cells called eosinophils were overly active. Researchers found that ME/CFS patients had significantly higher ECP levels than healthy controls, and most ME/CFS patients also tested positive for allergies. However, ME/CFS patients with allergies did not have higher ECP levels than those without allergies, suggesting the connection may be more complex than initially expected.

Frequency of deviant immunological test values in chronic fatigue syndrome patients.

Natelson, B H, Ellis, S P, Braonáin, P J et al.·Clinical and diagnostic laboratory immunology·1995

Researchers tested 11 different immune system markers in ME/CFS patients and compared them to fatigued people without ME/CFS. They found that three immune tests (protein A binding, Raji cell test, and complement proteins C3 or C4) showed different results between the groups. However, most other immune tests they looked at, including antibody levels and other complement markers, did not reliably distinguish ME/CFS patients from those with other causes of fatigue.

Human herpesvirus 6 and human herpesvirus 7 in chronic fatigue syndrome.

Di Luca, D, Zorzenon, M, Mirandola, P et al.·Journal of clinical microbiology·1995

Researchers looked for two common viruses (HHV-6 and HHV-7) in immune cells of ME/CFS patients and compared them to healthy people. They found that HHV-7 was equally common in both groups, but a specific type of HHV-6 called variant A was found more often in ME/CFS patients. This suggests that HHV-6 variant A may be connected to ME/CFS, though the study does not prove it causes the illness.

Seroepidemiology of chronic fatigue syndrome: a case-control study.

Mawle, A C, Nisenbaum, R, Dobbins, J G et al.·Clinical infectious diseases : an official publication of the Infectious Diseases Society of America·1995

Researchers tested people with ME/CFS and healthy control groups for antibodies to many common viruses, including herpesviruses and enteroviruses. They found no differences between the two groups—patients with ME/CFS did not have higher levels of antibodies to any of the viruses tested. This suggests that recent or past infection with these particular viruses is not a distinguishing feature of ME/CFS.

Prevalence of IgM antibodies to human herpesvirus 6 early antigen (p41/38) in patients with chronic fatigue syndrome.

Patnaik, M, Komaroff, A L, Conley, E et al.·The Journal of infectious diseases·1995

Researchers tested whether people with ME/CFS have more signs of a virus called human herpesvirus 6 (HHV-6) compared to healthy people. They found that 77% of ME/CFS patients had antibodies suggesting exposure to or active HHV-6 infection, compared to only 12% of healthy controls. This suggests HHV-6 may be more common in people with ME/CFS, though it's unclear whether the virus causes the illness or is simply more active in these patients.

Abnormalities of carnitine metabolism in chronic fatigue syndrome.

Majeed, T, de Simone, C, Famularo, G et al.·European journal of neurology·1995

This study examined carnitine, a substance that helps cells produce energy, in people with ME/CFS. Researchers found that while carnitine levels in the blood were normal, the levels inside immune cells were significantly lower in ME/CFS patients compared to healthy people. This finding suggests that ME/CFS patients might benefit from taking carnitine supplements to restore normal energy production.

Cell-mediated immune function and the outcome of chronic fatigue syndrome.

Wilson, A, Hickie, I, Lloyd, A et al.·International journal of immunopharmacology·1995

Researchers followed 103 ME/CFS patients for an average of 3.2 years to see if their immune system function predicted how well they would recover. Most patients improved over time, but about one-third remained unable to work. The study found that immune cell measurements taken at the start did not seem to predict who would get better or worse.

Clinical laboratory test findings in patients with chronic fatigue syndrome.

Bates, D W, Buchwald, D, Lee, J et al.·Archives of internal medicine·1995

Researchers compared blood test results from 579 ME/CFS patients with results from 147 healthy people. They found that ME/CFS patients were much more likely to have certain abnormal results, particularly immune-related changes like unusual white blood cells and immune complexes. However, no single test was abnormal enough in all patients to serve as a reliable diagnostic tool on its own.

Prevalence of human herpesvirus 6 variants A and B in patients with chronic fatigue syndrome.

Yalcin, S, Kuratsune, H, Yamaguchi, K et al.·Microbiology and immunology·1994

Researchers tested blood samples from 13 ME/CFS patients and 13 healthy people to see if they carried human herpesvirus 6 (HHV-6), a common virus that most people encounter in childhood. They found that over half of the ME/CFS patients had active HHV-6 in their blood, while none of the healthy controls did. The patients also had higher antibody levels, suggesting their immune systems were actively fighting the virus.

[Chronic fatigue syndrome--a controlled cross-sectional study].

Rasmussen, A K, Nielsen, H, Andersen, V et al.·Ugeskrift for laeger·1994

This study compared immune system markers in 21 people with ME/CFS to 21 healthy people matched by age and sex. Researchers found that certain immune cells in ME/CFS patients produced higher levels of specific immune signaling molecules, while antibody levels were slightly lower than normal. Overall, the study did not find clear evidence that ME/CFS is caused by a persistent viral infection or a severely damaged immune system.

Immunologic abnormalities associated with chronic fatigue syndrome.

Barker, E, Fujimura, S F, Fadem, M B et al.·Clinical infectious diseases : an official publication of the Infectious Diseases Society of America·1994

This study examined immune cells in the blood of ME/CFS patients and compared them to healthy people. Researchers found that ME/CFS patients had normal numbers of immune cells overall, but the cells showed signs of being overactive and tired. Most notably, patients had significantly reduced natural killer cell activity—these are immune cells that normally help fight infections and abnormal cells.

Psychobehavioral and immunological characteristics of adult people with chronic fatigue and patients with chronic fatigue syndrome.

Masuda, A, Nozoe, S I, Matsuyama, T et al.·Psychosomatic medicine·1994

This study compared immune system function and psychological stress levels in three groups: healthy people, those with chronic fatigue (but not ME/CFS), and patients with ME/CFS. All three groups showed differences in how stressed they felt, their activity levels, and how well their immune cells (specifically natural killer cells) worked. Importantly, the chronic fatigue group fell somewhere between healthy people and ME/CFS patients in terms of both psychological stress and immune function.

An approach to studies of cancer subsequent to clusters of chronic fatigue syndrome: use of data from the Nevada State Cancer Registry.

Levine, P H, Atherton, M, Fears, T et al.·Clinical infectious diseases : an official publication of the Infectious Diseases Society of America·1994

This study looked at whether people in Nevada who developed a CFS-like illness in the mid-1980s had higher rates of cancer, particularly brain tumors and lymphoma, in the years that followed. Researchers checked cancer registry records to see if there was a connection. They found a slight increase in brain tumors but no clear pattern for lymphoma, though they noted the brain tumor trend might reflect a nationwide pattern rather than something specific to CFS.

Simultaneous measurement of antibodies to Epstein-Barr virus, human herpesvirus 6, herpes simplex virus types 1 and 2, and 14 enteroviruses in chronic fatigue syndrome: is there evidence of activation of a nonspecific polyclonal immune response?

Manian, F A·Clinical infectious diseases : an official publication of the Infectious Diseases Society of America·1994

This study looked at whether people with ME/CFS have higher levels of antibodies (immune proteins that fight viruses) to multiple different viruses compared to healthy people. Researchers tested blood samples from 20 ME/CFS patients and 20 healthy controls for antibodies to five different viruses. They found that most ME/CFS patients had elevated antibodies to at least one virus, but the pattern didn't suggest a generalized immune overreaction affecting all viruses equally.

Chronic fatigue syndrome--a controlled cross sectional study.

Rasmussen, A K, Nielsen, H, Andersen, V et al.·The Journal of rheumatology·1994

Researchers compared immune system markers in 21 people with ME/CFS to 21 healthy controls to see if immune problems might cause the illness. They found that people with ME/CFS produced higher levels of certain immune signaling molecules and had slightly different antibody patterns, but overall immune system differences between the groups were small. The study suggests the immune system may be out of balance in ME/CFS, but doesn't prove this imbalance actually causes the disease.

[Chronic fatigue syndrome: immune dysfunction, role of pathogens and toxic agents and neurological and cardial changes].

Hilgers, A, Frank, J·Wiener medizinische Wochenschrift (1946)·1994

This study examined 375 patients with ME/CFS to understand what goes wrong with their immune systems and which infections might be involved. Researchers found that most patients had problems with immune cell function, signs of past viral infections (especially Epstein-Barr virus), and imbalances in immune chemicals. The study suggests ME/CFS may be connected to autoimmune problems and multiple infections.

High titers of anti-Epstein-Barr virus DNA polymerase are found in patients with severe fatiguing illness.

Natelson, B H, Ye, N, Moul, D E et al.·Journal of medical virology·1994