Evidence browser

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.

Discriminating Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and comorbid conditions using metabolomics in UK Biobank.

Huang, Katherine, G C de Sá, Alex, Thomas, Natalie et al.·Communications medicine·2024

Researchers studied blood samples from nearly 1,200 people with ME/CFS and compared them to people with other common conditions like depression, asthma, and thyroid problems. They found nine specific markers in the blood that, combined with basic health information, could identify ME/CFS patients about 70% of the time. This blood test approach could eventually help doctors diagnose ME/CFS more easily, since there is currently no definitive test for the condition.

E2 ModerateMechanismPEM unclearMechanistic

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.

E2 ModerateCohortPEM not requiredObservational

Association between fatigue, peripheral serotonin, and L-carnitine in hypothyroidism and in chronic fatigue syndrome.

Raij, Tommi, Raij, Kari·Frontiers in endocrinology·2024

This study examined whether a supplement called L-carnitine could help reduce fatigue by increasing serotonin levels in the blood. Researchers tracked 12 people with ME/CFS and 40 people with hypothyroidism who were experiencing fatigue, measuring their serotonin and fatigue levels before and after taking L-carnitine for 7 weeks. They found that L-carnitine increased serotonin levels significantly and fatigue decreased by about half in both groups, suggesting a possible connection between low serotonin and fatigue.

BiomarkersEnergy Metabolism

Association of circulating biomarkers with illness severity measures differentiates myalgic encephalomyelitis/chronic fatigue syndrome and post-COVID-19 condition: a prospective pilot cohort study.

Domingo, Joan Carles, Battistini, Federica, Cordobilla, Begoña et al.·Journal of translational medicine·2024

This study compared blood markers and body responses between people with ME/CFS, people with long COVID, and healthy controls. Researchers found that people with ME/CFS had distinct patterns of inflammation and blood vessel dysfunction compared to long COVID patients, suggesting these are different conditions with different underlying problems. By measuring specific proteins in the blood and testing how the body responds to positional changes, researchers could tell the two patient groups apart.

Sex and disease severity-based analysis of steroid hormones in ME/CFS.

Pipper, Cornelia, Bliem, Linda, León, Luis E et al.·Journal of endocrinological investigation·2024

Researchers measured hormone levels in the blood of ME/CFS patients and compared them to healthy people. They found that certain hormones—including cortisol-related compounds and progesterone—were different in people with ME/CFS, and the differences varied depending on whether patients had mild/moderate or severe disease and their sex. These hormone patterns might help doctors better identify and categorize ME/CFS in the future.

E2 ModerateMechanismPEM not requiredMechanistic

Manual Therapy Improves Fibromyalgia Symptoms by Downregulating SIK1.

Bonastre-Férez, Javier, Giménez-Orenga, Karen, Falaguera-Vera, Francisco Javier et al.·International journal of molecular sciences·2024

This study tested whether a specialized hands-on therapy treatment could help fibromyalgia patients and discovered why it might work. Researchers found that the treatment lowered levels of a specific gene called SIK1 in patients' blood cells, and this change was linked to improvements in pain, fatigue, and quality of life. Importantly, this gene change only happened in fibromyalgia patients who received the treatment—not in healthy people who got the same therapy.

Circulating microRNA expression signatures accurately discriminate myalgic encephalomyelitis from fibromyalgia and comorbid conditions.

Nepotchatykh, Evguenia, Caraus, Iurie, Elremaly, Wesam et al.·Scientific reports·2023

Researchers studied tiny molecules called microRNAs in the blood to see if they could tell the difference between ME/CFS, fibromyalgia, and people who have both conditions. They found that each condition has a unique pattern of these microRNAs, like a biological fingerprint. Using these patterns, they created a computer model that could accurately identify which condition a person has, which could help with proper diagnosis.

Circulating miRNAs Expression in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Soffritti, Irene, Gravelsina, Sabine, D'Accolti, Maria et al.·International journal of molecular sciences·2023

Researchers tested whether six small molecules called microRNAs (miRNAs) in the blood could help identify people with ME/CFS. They compared blood samples from 40 ME/CFS patients with 20 healthy people and found that five miRNAs were more abundant in patients' blood while one was less abundant. Interestingly, the levels of these molecules matched how severe each patient's symptoms were, suggesting they could potentially be used as a blood test to help diagnose ME/CFS.

E2 ModerateCohortPEM unclearObservational

Utility of Serum Ferritin for Predicting Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in Patients with Long COVID.

Yamamoto, Yukichika, Otsuka, Yuki, Tokumasu, Kazuki et al.·Journal of clinical medicine·2023

This study looked at 234 people with long COVID to understand why some developed ME/CFS (a severe fatigue condition) while others didn't. Researchers found that people who developed ME/CFS had significantly higher levels of ferritin, a protein that stores iron, in their blood compared to those with long COVID fatigue alone or no fatigue. The finding was especially strong in women, suggesting that a simple blood test measuring ferritin might help predict who is at risk of developing ME/CFS after COVID-19.

Unsupervised Cluster Analysis Reveals Distinct Subtypes of ME/CFS Patients Based on Peak Oxygen Consumption and SF-36 Scores.

Lacasa, Marcos, Launois, Patricia, Prados, Ferran et al.·Clinical therapeutics·2023

This study examined whether oxygen consumption during an exercise test could help identify different types of ME/CFS patients. Researchers used questionnaire responses from 2,347 ME/CFS patients and then tested their findings in 92 patients who completed an exercise test. They found that patient responses on a quality-of-life survey directly matched up with how much oxygen their bodies could use during exercise, suggesting that low oxygen consumption may be a useful marker for identifying ME/CFS severity.

E2 ModerateCohortPEM not requiredObservational

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.

E2 ModerateCohortPEM not requiredCross-Sectional

Distinguishing features of long COVID identified through immune profiling.

Klein, Jon, Wood, Jamie, Jaycox, Jillian R et al.·Nature·2023

Researchers studied 275 people with and without long COVID to understand what happens in the immune system. They found that people with long COVID have different patterns of immune cells and antibodies, including stronger responses to past viral infections like Epstein-Barr virus, and lower levels of the stress hormone cortisol. Using computer analysis, they identified specific immune markers that could help identify who has long COVID.

Evidence of a Novel Mitochondrial Signature in Systemic Sclerosis Patients with Chronic Fatigue Syndrome.

van Eeden, Charmaine, Redmond, Desiree, Mohazab, Naima et al.·International journal of molecular sciences·2023

This study looked at people with a connective tissue disease called systemic sclerosis who also experience severe fatigue (ME/CFS symptoms). Researchers found that fatigued patients had different patterns in how their cells' energy-producing structures (mitochondria) work compared to non-fatigued patients. These differences involved specific genes related to energy production, suggesting that measuring these genes might help doctors identify which systemic sclerosis patients have ME/CFS.

E2 ModerateCohortPEM requiredLongitudinal

Long-term symptom severity and clinical biomarkers in post-COVID-19/chronic fatigue syndrome: results from a prospective observational cohort.

Legler, Franziska, Meyer-Arndt, Lil, Mödl, Lukas et al.·EClinicalMedicine·2023

This study followed 106 people with long-term fatigue after COVID-19 for up to 20 months to see how they recovered over time. Researchers found that some patients met the diagnostic criteria for ME/CFS and had persistent, severe symptoms including fatigue and post-exertional malaise (worsening after activity), while others improved more substantially. Lower muscle strength at the start of illness was linked to ongoing symptoms, especially in those with ME/CFS.

BiomarkersImmune SystemPost-Exertional Malaise

E2 ModerateCohortPEM not requiredCross-Sectional

A Causal-Pathway Phenotype of Chronic Fatigue Syndrome due to Hemodialysis in Patients with End-Stage Renal Disease.

Asad, Halah Nori, Al-Hakeim, Hussein Kadhem, Moustafa, Shatha Rouf et al.·CNS & neurological disorders drug targets·2023

This study looked at patients with severe kidney disease who need dialysis (a machine that cleans their blood) and found they often experience extreme fatigue and other symptoms similar to ME/CFS, such as muscle pain, sleep problems, and brain fog. Researchers measured various substances in the blood and found that fatigue was linked to anemia (low blood iron), poor nutrition, and certain protein imbalances caused by the dialysis treatment itself. The more dialysis sessions patients needed, the worse their fatigue tended to be.

E2 ModerateCohortPEM not requiredCross-Sectional

The physio-affective phenome of major depression is strongly associated with biomarkers of astroglial and neuronal projection toxicity which in turn are associated with peripheral inflammation, insulin resistance and lowered calcium.

Al-Hakeim, Hussein Kadhem, Al-Naqeeb, Tabarek Hadi, Almulla, Abbas F et al.·Journal of affective disorders·2023

This study examined whether brain and nerve damage markers in the blood are connected to depression symptoms and other physical complaints. Researchers measured several proteins in the blood of people with depression and compared them to healthy controls, finding that markers of brain cell and nerve damage—along with inflammation and insulin resistance—together explained about 61% of the severity of depression, anxiety, fatigue, and physical symptoms.

NeuroinflammationBiomarkers

E2 ModerateCohortPEM requiredCross-Sectional

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.

E2 ModerateCohortPEM requiredLongitudinal

One-year follow-up of young people with ME/CFS following infectious mononucleosis by Epstein-Barr virus.

Pricoco, Rafael, Meidel, Paulina, Hofberger, Tim et al.·Frontiers in pediatrics·2023

This study followed 25 young people (12 teenagers and 13 young adults) who developed ME/CFS after having infectious mononucleosis caused by Epstein-Barr virus. Researchers checked on their symptoms and quality of life at the start, 6 months, and 12 months later. Teenagers showed better improvement over the year, with more than half no longer meeting ME/CFS criteria, while young adults continued to have severe symptoms with little improvement.

Severe MEBiomarkersPost-Exertional Malaise

E2 ModerateCohortPEM not required

Metabolomic Evidence for Peroxisomal Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Che, Xiaoyu, Brydges, Christopher R, Yu, Yuanzhi et al.·International journal of molecular sciences·2022

Researchers found that people with ME/CFS have abnormal levels of certain fats and chemicals in their blood compared to healthy people. Specifically, they had lower levels of protective fats called plasmalogens and phospholipids, but higher levels of compounds called dicarboxylic acids. These chemical differences were so distinctive that a computer program could identify ME/CFS patients from their blood work with reasonable accuracy.