Evidence browser

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.

E2 ModerateCohortPEM unclearCase-Control

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.

No difference in serum levels of B-cell activating receptor and antibodies against cytolethal distending toxin B and flagellin in post-infectious irritable bowel syndrome and chronic fatigue syndrome after Giardia infection.

Hanevik, Kurt, Saghaug, Christina, Aaland, Maren et al.·JGH open : an open access journal of gastroenterology and hepatology·2022

This study looked for three potential biological markers (BAFF, anti-CdtB, and anti-flagellin antibodies) in the blood of people who developed ME/CFS and/or IBS after a Giardia infection. Researchers compared these markers in patients to healthy controls but found no significant differences between the groups. The findings suggest these three markers are not useful for diagnosing ME/CFS or IBS.

Dysregulated autoantibodies targeting vaso- and immunoregulatory receptors in Post COVID Syndrome correlate with symptom severity.

Sotzny, Franziska, Filgueiras, Igor Salerno, Kedor, Claudia et al.·Frontiers in immunology·2022

This study looked at whether certain antibodies in the blood—proteins the immune system makes that sometimes attack the body's own tissues—might explain why some people with long COVID develop ME/CFS symptoms like severe fatigue and blood flow problems. Researchers compared antibody levels in 80 patients with long COVID (40 with ME/CFS) against healthy people and found that patients had different patterns of these antibodies, particularly ones affecting blood vessels and the nervous system. The severity of fatigue and blood pressure/temperature regulation problems seemed connected to lower levels of a specific antibody (ADRB2), suggesting the immune system's dysregulation may play a role in these symptoms.

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.

E2 ModerateCohortPEM requiredObservational

A prospective observational study of post-COVID-19 chronic fatigue syndrome following the first pandemic wave in Germany and biomarkers associated with symptom severity.

Kedor, Claudia, Freitag, Helma, Meyer-Arndt, Lil et al.·Nature communications·2022

This study followed 42 people with long-lasting fatigue after COVID-19 infection for six months and compared them to people with similar chronic fatigue from other causes. Most participants experienced moderate to severe fatigue that interfered with daily life. The researchers found that many of these post-COVID patients had reduced hand grip strength and blood markers suggesting possible inflammation and poor blood flow, which may help explain why their bodies struggle to recover.

Immune SystemPost-Exertional Malaise

E2 ModerateCohortPEM not requiredObservational

Undetected Jawbone Marrow Defects as Inflammatory and Degenerative Signaling Pathways: Chemokine RANTES/CCL5 as a Possible Link Between the Jawbone and Systemic Interactions?

Lechner, Johann, Schmidt, Marlene, von Baehr, Volker et al.·Journal of inflammation research·2021

This study examined jawbone abnormalities in 301 patients with various chronic illnesses, including ME/CFS. Researchers found that patients with bone loss in the jawbone had elevated levels of a chemical messenger called RANTES/CCL5, which promotes inflammation. These findings were consistent across all disease groups studied, suggesting that jawbone problems may contribute to systemic inflammation in multiple conditions.

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.

E2 ModerateCohortPEM unclearObservational

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.

BiomarkersEnergy MetabolismImmune System

E2 ModerateCohortPEM not requiredCross-Sectional

Lowered serum cesium levels in schizophrenia: association with immune-inflammatory biomarkers and cognitive impairments.

Almulla, Abbas F, Moustafa, Shatha R, Al-Dujaili, Arafat H et al.·Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999)·2021

This study looked at a mineral called cesium in the blood of people with schizophrenia and compared it to healthy people. They found that people with schizophrenia had lower cesium levels, and this was connected to cognitive problems (like memory and thinking difficulties), fatigue symptoms, and signs of immune system activity. The researchers suggest that low cesium might contribute to some of the symptoms seen in schizophrenia.

E2 ModerateCohortPEM not requiredCross-Sectional

The antinuclear antibody dense fine speckled pattern and possible clinical associations: An indication of a proinflammatory microenvironment.

Lundgren, Mia C, Sapkota, Smarika, Peterson, Daniel J et al.·Journal of immunological methods·2021

This study looked at 425 patients who tested positive for a specific antibody pattern called ANA-DFS on a common autoimmune screening test. The researchers wanted to understand what conditions this pattern is associated with. They found that while some patients had known autoimmune diseases, many others had chronic fatigue syndrome, fibromyalgia, skin problems, or allergic conditions, suggesting this antibody pattern may indicate a generally inflamed immune system rather than one specific disease.

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.

E2 ModerateCohortPEM requiredCase-Control

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.

E2 ModerateCohortPEM not requiredLongitudinal

Inflammation-type dysbiosis of the oral microbiome associates with the duration of COVID-19 symptoms and long COVID.

Haran, John P, Bradley, Evan, Zeamer, Abigail L et al.·JCI insight·2021

This study looked at bacteria in the mouth of people with COVID-19 to understand why some people develop long COVID. Researchers found that people with long COVID had higher levels of inflammation-causing bacteria, particularly types called Prevotella and Veillonella. Interestingly, the oral bacteria patterns in long COVID patients resembled those seen in chronic fatigue syndrome patients, suggesting the microbiome may play a role in prolonged illness.

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.

Sex-Based Differences in Plasma Autoantibodies to Central Nervous System Proteins in Gulf War Veterans versus Healthy and Symptomatic Controls.

Abou-Donia, Mohamed B, Krengel, Maxine H, Lapadula, Elizabeth S et al.·Brain sciences·2021

Researchers found that Gulf War veterans with Gulf War illness have abnormal immune proteins in their blood that attack brain cells, and these patterns differ between men and women. The study also found that these same immune markers can help distinguish Gulf War illness from other similar conditions like ME/CFS and IBS. This discovery is important because it offers a possible objective blood test that doctors could use to identify and diagnose these difficult-to-recognize illnesses.

E2 ModerateCohortPEM not requiredCross-Sectional

Co-occurrence of immune-mediated conditions and endometriosis among adolescents and adult women.

Shafrir, Amy L, Palmor, Marissa C, Fourquet, Jessica et al.·American journal of reproductive immunology (New York, N.Y. : 1989)·2021

This study looked at whether young women and adolescents with endometriosis (a painful condition where tissue grows outside the uterus) are more likely to have immune system problems like allergies, asthma, or chronic fatigue. Researchers compared 551 women with surgically confirmed endometriosis to 652 women without it and found that those with endometriosis were significantly more likely to have chronic fatigue syndrome, fibromyalgia, or a history of mononucleosis. The more immune-related conditions a woman had, the higher her chances of also having endometriosis.

E2 ModerateCohortPEM requiredCase-Control

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.

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.