Evidence browser

Inflammation From Peripheral Organs to the Brain: How Does Systemic Inflammation Cause Neuroinflammation?

Sun, Yuanjie, Koyama, Yoshihisa, Shimada, Shoichi·Frontiers in aging neuroscience·2022

This review explores how inflammation in the body's organs—like the gut, lungs, or joints—can trigger inflammation in the brain. The authors describe several pathways by which this happens, including damage to the protective barrier around the brain, activation of immune cells in the brain, and communication through nerves connecting organs to the brain. ME/CFS is highlighted as one disease where this peripheral-to-brain inflammation mechanism may be important.

E3 PreliminaryDiagnosticPEM unclearMethods-Paper

Identification of transient receptor potential melastatin 3 proteotypic peptides employing an efficient membrane protein extraction method for natural killer cells.

Magawa, Chandi T, Eaton-Fitch, Natalie, Balinas, Cassandra et al.·Frontiers in physiology·2022

Researchers developed a better way to extract and study proteins from immune cells called natural killer cells in ME/CFS patients. They focused on a specific protein channel called TRPM3, which may play a role in ME/CFS. This study shows they can now reliably detect this protein, which opens the door for future research to understand how it might be different in ME/CFS.

E3 PreliminaryCohortPEM not requiredCase-Control

New Clinical Phenotype of the Post-Covid Syndrome: Fibromyalgia and Joint Hypermobility Condition.

Gavrilova, Natalia, Soprun, Lidiia, Lukashenko, Maria et al.·Pathophysiology : the official journal of the International Society for Pathophysiology·2022

This study describes a pattern found in some people who developed fibromyalgia (widespread pain) after COVID-19 infection. The researchers noticed that young women with loose, flexible joints who had COVID-19 and a specific tendon injury were more likely to develop fibromyalgia along with signs of inflammation. The study presents three patient cases that fit this pattern, suggesting COVID-19 may trigger fibromyalgia in people whose connective tissues are already prone to damage.

Long COVID OverlapImmune System

Chronic post-COVID-19 syndrome and chronic fatigue syndrome: Is there a role for extracorporeal apheresis?

Bornstein, Stefan R, Voit-Bak, Karin, Donate, Timo et al.·Molecular psychiatry·2022

Some people who had COVID-19 continue to experience fatigue and breathing problems long after recovering from the infection, a condition called long-COVID. This pattern of ongoing symptoms looks similar to ME/CFS, another condition that causes persistent fatigue. Researchers found that both conditions may involve the body producing antibodies (immune proteins) that attack certain nerve receptors. A treatment called extracorporeal apheresis, which filters blood to remove these harmful antibodies, showed promise in improving symptoms in ME/CFS patients and might also help those with long-COVID.

At the Root of 3 "Long" Diseases: Persistent Antigens Inflicting Chronic Damage on the Brain and Other Organs in Gulf War Illness, Long-COVID-19, and Chronic Fatigue Syndrome.

James, Lisa M, Georgopoulos, Apostolos P·Neuroscience insights·2022

This review explores why some people develop long-lasting illnesses after exposure to viruses or bacteria, while others recover normally. The researchers propose that certain infections may persist in the body longer in people with specific immune system markers (HLA types), potentially causing ongoing damage to the brain and other organs. They suggest this mechanism might explain symptoms seen in ME/CFS, long-COVID, and Gulf War Illness.

EBV/HHV-6A dUTPases contribute to myalgic encephalomyelitis/chronic fatigue syndrome pathophysiology by enhancing TFH cell differentiation and extrafollicular activities.

Cox, Brandon S, Alharshawi, Khaled, Mena-Palomo, Irene et al.·JCI insight·2022

This study found that some people with ME/CFS have abnormal immune responses linked to past infections with Epstein-Barr virus (EBV) and human herpesvirus 6A (HHV-6A). The researchers discovered that proteins from these viruses may trigger the immune system to produce excess amounts of certain signaling molecules, leading to confused immune cell behavior. This suggests a possible biological mechanism for how these common viruses might contribute to ME/CFS symptoms in some patients.

E3 PreliminaryCohortPEM unclearCase-Control

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: First Described Complication after Gam-COVID-Vac Vaccine.

Manysheva, Ksenia, Sherman, Mikhail, Zhukova, Natalia et al.·Psychiatria Danubina·2022

This report describes one case of a 25-year-old woman who developed ME/CFS symptoms about 10 days after receiving the Sputnik V COVID-19 vaccine. She experienced severe fatigue, muscle pain, and difficulty moving. This is the first documented case linking ME/CFS to this particular vaccine, though it remains unclear whether the vaccine caused the condition or if it occurred by coincidence.

Phenotypic characteristics of peripheral immune cells of Myalgic encephalomyelitis/chronic fatigue syndrome via transmission electron microscopy: A pilot study.

Jahanbani, Fereshteh, Maynard, Rajan D, Sing, Justin Cyril et al.·PloS one·2022

Researchers used a powerful microscope to examine immune cells from people with ME/CFS and found several abnormalities. They observed that immune cells from ME/CFS patients died more frequently when activated, had swollen energy-producing structures (mitochondria), and in one severely ill patient, contained unusual fat-like accumulations. These cellular changes suggest that ME/CFS involves real, measurable damage to immune system function.

Elevated ATG13 in serum of patients with ME/CFS stimulates oxidative stress response in microglial cells via activation of receptor for advanced glycation end products (RAGE).

Gottschalk, Gunnar, Peterson, Daniel, Knox, Konstance et al.·Molecular and cellular neurosciences·2022

Researchers found that people with ME/CFS have higher levels of a protein called ATG13 in their blood compared to healthy people. When they tested this protein on brain immune cells in the lab, it triggered the production of harmful molecules called free radicals (oxidative stress). This suggests that a breakdown in the body's cellular recycling system (autophagy) might contribute to the inflammation and stress response seen in ME/CFS.

Immune SystemGut MicrobiomeNeuroinflammation

Mucosal Immunity and the Gut-Microbiota-Brain-Axis in Neuroimmune Disease.

Sterling, Kathryn G, Dodd, Griffin Kutler, Alhamdi, Shatha et al.·International journal of molecular sciences·2022

This review article examines the connection between gut bacteria, immunity, and the brain in diseases like ME/CFS. The authors explain that the bacteria in our gut can communicate with our brain through chemical signals and nerves, but this communication can be disrupted in certain illnesses. They focus on how the immune system in the gut lining controls which bacteria thrive there, and how changes in these bacterial communities might contribute to neuroimmune diseases.

E3 PreliminaryMechanismPEM not requiredMechanistic

Sciatic-Vagal Nerve Stimulation by Electroacupuncture Alleviates Inflammatory Arthritis in Lyme Disease-Susceptible C3H Mice.

Akoolo, Lavoisier, Djokic, Vitomir, Rocha, Sandra C et al.·Frontiers in immunology·2022

This study tested whether electroacupuncture (a needle-based treatment that uses electrical stimulation) could reduce joint inflammation and symptoms in mice with Lyme disease. The researchers found that electroacupuncture reduced inflammation markers and immune cells in the joints, even though it didn't eliminate the Lyme bacteria itself. The anti-inflammatory effects lasted even after treatment stopped, suggesting this approach might help people with long-lasting Lyme disease symptoms.

Aberrations in the Cross-Talks Among Redox, Nuclear Factor-κB, and Wnt/β-Catenin Pathway Signaling Underpin Myalgic Encephalomyelitis and Chronic Fatigue Syndrome.

Maes, Michael, Kubera, Marta, Kotańska, Magdalena·Frontiers in psychiatry·2022

This study examined proteins and metabolites in ME/CFS patients to understand how the disease works at a molecular level. Researchers found that ME/CFS involves problems with three interconnected cellular systems: how cells handle harmful oxidative stress, how the immune system responds through inflammation, and how cells communicate through a pathway called Wnt/β-catenin. The study suggests ME/CFS may be triggered by various causes—like infections or toxic exposures—but they all damage these same three systems.

E3 PreliminaryMechanismPEM not requiredCross-Sectional

No Signs of Neuroinflammation in Women With Chronic Fatigue Syndrome or Q Fever Fatigue Syndrome Using the TSPO Ligand [11C]-PK11195.

Raijmakers, Ruud, Roerink, Megan, Keijmel, Stephan et al.·Neurology(R) neuroimmunology & neuroinflammation·2022

Researchers used a specialized brain scan to look for signs of inflammation in the brains of women with ME/CFS and Q fever fatigue syndrome, compared to healthy women. The scan didn't find evidence of the type of brain inflammation they were looking for, which contradicts some earlier research suggesting inflammation might play a role in these conditions.

BiomarkersImmune SystemNeuroinflammation

Circadian rhythm disruption in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Implications for the post-acute sequelae of COVID-19.

McCarthy, Michael J·Brain, behavior, & immunity - health·2022

This review examines whether disrupted body clocks (circadian rhythms) contribute to ME/CFS symptoms like fatigue, sleep problems, and cognitive difficulties. The authors focus on a specific immune molecule called TGFB that may interfere with the body's natural daily rhythms. They suggest that COVID-19 infections may cause similar circadian disruptions, potentially explaining why some people develop long COVID symptoms that resemble ME/CFS.

Molecular Mechanisms of Neuroinflammation in ME/CFS and Long COVID to Sustain Disease and Promote Relapses.

Tate, Warren, Walker, Max, Sweetman, Eiren et al.·Frontiers in neurology·2022

This paper proposes that ME/CFS and Long COVID may share a common mechanism: neuroinflammation (brain-centred inflammation) that develops after an initial stressor—such as a viral infection—crosses into the brain and disrupts normal immune control. The authors hypothesise that this brain-based process sustains the illness and prevents recovery, explaining why symptoms persist and relapse. However, this is a theoretical review, not an experimental study, so the proposed mechanisms remain unproven.

Bioinformatics and systems biology approach to identify the pathogenetic link of Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Lv, Yongbiao, Zhang, Tian, Cai, Junxiang et al.·Frontiers in immunology·2022

Researchers compared the genes involved in Long COVID (lasting symptoms after COVID-19 infection) and ME/CFS to see if they share common biological causes. They found 9 genes that appear in both conditions and identified five key proteins that may be driving the shared symptoms. The study suggests these conditions may have overlapping mechanisms, pointing toward potential new treatments worth testing in future research.

Epipharyngeal Abrasive Therapy (EAT) Reduces the mRNA Expression of Major Proinflammatory Cytokine IL-6 in Chronic Epipharyngitis.

Nishi, Kensuke, Yoshimoto, Shohei, Nishi, Soichiro et al.·International journal of molecular sciences·2022

This study looked at a Japanese treatment called Epipharyngeal Abrasive Therapy (EAT) that targets chronic inflammation in the epipharynx (the area behind your nasal cavity). The researchers found that patients who received EAT had significantly lower levels of IL-6, a key inflammatory molecule linked to ME/CFS symptoms, compared to those who didn't receive the treatment. This suggests that reducing inflammation in this specific area might help improve systemic symptoms in ME/CFS and similar conditions.

E3 PreliminaryReviewPEM not requiredReview-Narrative

Breast implant illness: scientific evidence of its existence.

Cohen Tervaert, J W, Mohazab, N, Redmond, D et al.·Expert review of clinical immunology·2022

This review examined whether silicone breast implants cause a condition called breast implant illness (BII), which includes symptoms like chronic fatigue, joint pain, muscle pain, and brain fog. The authors concluded that there is a causal link between silicone implants and these systemic symptoms in some women, and that removing the implants typically resolves the symptoms.

E3 PreliminaryReviewPEM not requiredReview-Narrative

[Mechanism of acupuncture and moxibustion in treatment of chronic fatigue syndrome from perspective of intestinal flora].

Li, Chao-Ran, Sun, Zhong-Ren, Wang, Yu-Lin et al.·Zhongguo zhen jiu = Chinese acupuncture & moxibustion·2022

This study explores how gut bacteria may contribute to chronic fatigue syndrome and suggests that acupuncture and moxibustion (traditional Chinese medicine techniques) might help by restoring healthy gut bacteria. The researchers believe that an imbalance in gut bacteria can trigger inflammation and metabolism problems in ME/CFS patients, and that these traditional treatments could reduce fatigue by improving gut health and communication between the gut and brain.

Immune SystemGut Microbiome

Bioenergetic and Proteomic Profiling of Immune Cells in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients: An Exploratory Study.

Fernandez-Guerra, Paula, Gonzalez-Ebsen, Ana C, Boonen, Susanne E et al.·Biomolecules·2021

This study looked at how cells in ME/CFS patients produce and use energy differently than in healthy people. Researchers examined immune cells from six ME/CFS patients and found that these cells have lower efficiency in their mitochondria (the 'power plants' of cells) and struggle to produce enough energy to meet their needs. This energy shortage in cells may help explain why ME/CFS patients experience severe fatigue.