Immune Dysregulation

Long COVID OverlapImmune Dysregulation

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.

Metabolic DysfunctionImmune Dysregulation

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.

BiomarkersCognitive ImpairmentPost-Exertional MalaiseImmune Dysregulation

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.

Autonomic Nervous SystemImmune Dysregulation

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.

BiomarkersNeuroinflammationImmune Dysregulation

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.

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.

Post-Exertional MalaiseImmune DysregulationGut Microbiome

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.

E0 ConsensusPEM ?PreliminaryReviewed

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.

BiomarkersImmune Dysregulation

Metabolic DysfunctionBiomarkersPost-Exertional MalaiseImmune Dysregulation

[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.

BiomarkersImmune Dysregulation

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.

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.

Metabolic DysfunctionImmune Dysregulation

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.

NeuroinflammationImmune Dysregulation

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.

Cognitive ImpairmentPost-Exertional MalaiseImmune Dysregulation

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.

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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.

E0 ConsensusPEM ?Moderate confidenceMachine draft

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.

E0 ConsensusPEM ✓Moderate confidenceMachine draft

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.

Cognitive ImpairmentPost-Exertional MalaiseImmune Dysregulation

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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.

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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.

E0 ConsensusPEM ✓Moderate confidenceMachine draft

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.

Metabolic DysfunctionNeuroinflammationPost-Exertional MalaiseImmune Dysregulation

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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.

Immune DysregulationBiomarkers

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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.

Immune DysregulationInterventions

E2 ModeratePEM ✓Moderate confidenceMachine draft

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.

BiomarkersNeuroinflammationImmune Dysregulation

E2 ModeratePEM ✓Moderate confidenceMachine draft

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.

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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.

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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.

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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.

E3 PreliminaryPEM ?PreliminaryReviewed

Potential pathophysiological role of the ion channel TRPM3 in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and the therapeutic effect of low-dose naltrexone.

Löhn, Matthias, Wirth, Klaus Josef·Journal of translational medicine·2024

This study explores how a specific ion channel called TRPM3, which helps control pain signals and immune cell function, may not work properly in ME/CFS patients. The researchers found that immune cells called natural killer cells have reduced function due to TRPM3 problems, and a medication called low-dose naltrexone (LDN) may help restore this function in laboratory tests. This could explain why some ME/CFS patients report feeling better with LDN treatment.

Single-cell transcriptomics of the immune system in ME/CFS at baseline and following symptom provocation.

Vu, Luyen Tien, Ahmed, Faraz, Zhu, Hongya et al.·Cell reports. Medicine·2024

Researchers used advanced technology to examine immune cells from ME/CFS patients and healthy controls, both at rest and after exercise. They found that ME/CFS patients have problems with a type of immune cell called monocytes that appear abnormal and may be moving into tissues inappropriately. After exercise, patients showed additional problems with platelets (cells involved in blood clotting), suggesting the disease involves multiple layers of immune system dysfunction.

E3 PreliminaryPEM ✗Moderate confidenceReviewed

Oxidative stress is a shared characteristic of ME/CFS and Long COVID.

Shankar, Vishnu, Wilhelmy, Julie, Curtis, Ellis J et al.·Proceedings of the National Academy of Sciences of the United States of America·2025

Researchers found that both ME/CFS and Long COVID patients have higher levels of oxidative stress—a harmful buildup of unstable molecules—in their immune cells, particularly in a type of white blood cell called memory T cells. The study identified specific problems with how the body clears this oxidative stress and showed that the existing medication metformin might help reduce overgrowth of these immune cells. Importantly, they discovered these problems show different patterns in men and women, suggesting that sex-specific treatment approaches may be needed.

E3 PreliminaryPEM ?PreliminaryReviewed

Autoantibody targeting therapies in post COVID syndrome and myalgic encephalomyelitis/chronic fatigue syndrome.

Wohlrab, Felix, Eltity, Mailam, Ufer, Friederike et al.·Expert opinion on biological therapy·2025

This article reviews how certain immune system proteins called autoantibodies—which the body mistakenly makes against itself—may contribute to both long COVID and ME/CFS. The authors discuss different treatment approaches that aim to reduce or neutralize these harmful autoantibodies. This editorial examines the current evidence and potential of these new therapies to help patients with these conditions.

E3 PreliminaryPEM ✗PreliminaryReviewed

HLA and pathogens in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and other post-infection conditions.

Georgopoulos, Apostolos P, James, Lisa M, Peterson, Philip K·Scientific reports·2025

This study explores why some people develop ME/CFS after viral infections while others don't. Researchers looked at immune system genes (HLA types) and tested how well they recognize and fight nine common human herpes viruses. They found that people with certain HLA types have weak immune recognition of these viruses, potentially allowing the viruses to persist and cause ME/CFS, while people with other HLA types have strong recognition and protection.

E3 PreliminaryPEM ?PreliminaryReviewed

Heat vs. Fatigue: Hyperthermia as a Possible Treatment Option for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Hochecker, Barbara, Matt, Katja, Scherer, Melanie et al.·International journal of molecular sciences·2025

This small pilot study looked at how heat treatment (whole-body hyperthermia) affected immune cells from 9 people with ME/CFS. Researchers found that ME/CFS patients' cells showed signs of being overactive in certain ways compared to healthy people, and that heat treatment seemed to help normalize some of these cellular patterns. While these early results are promising, much larger studies are needed to confirm whether heat therapy could be a useful treatment.

Metabolic DysfunctionPost-Exertional MalaiseImmune Dysregulation

Heightened innate immunity may trigger chronic inflammation, fatigue and post-exertional malaise in ME/CFS.

Che, Xiaoyu, Ranjan, Amit, Guo, Cheng et al.·medRxiv : the preprint server for health sciences·2025

This study found that people with ME/CFS may have an overactive immune system that responds too strongly to germs and infections. The research showed problems with how the body produces energy and manages inflammation, and these problems got worse after exercise in ME/CFS patients but not in healthy people. The findings suggest multiple biological systems are working abnormally in ME/CFS, which could help doctors develop better treatments.

Metabolic DysfunctionPost-Exertional MalaiseImmune Dysregulation

Heightened innate immunity may trigger chronic inflammation, fatigue and post-exertional malaise in ME/CFS.

Che, Xiaoyu, Ranjan, Amit, Guo, Cheng et al.·npj metabolic health and disease·2025

This study examined blood samples and immune responses in ME/CFS patients to understand why they experience extreme fatigue and feeling worse after activity. Researchers found that patients' immune systems overreact to germs, their bodies have trouble producing energy efficiently, and they have several chemical imbalances in their blood. These problems got worse after exercise and matched how sick patients felt.

BiomarkersCognitive ImpairmentPost-Exertional MalaiseImmune Dysregulation

Dissecting the genetic complexity of myalgic encephalomyelitis/chronic fatigue syndrome via deep learning-powered genome analysis.

Zhang, Sai, Jahanbani, Fereshteh, Chander, Varuna et al.·medRxiv : the preprint server for health sciences·2025

Researchers used advanced artificial intelligence to analyze the genes of ME/CFS patients and discovered 115 genes that may contribute to the disease. They found that people with ME/CFS have lower levels of these risk genes active in their immune cells and nervous system. This genetic analysis could eventually help doctors diagnose ME/CFS more accurately and identify new treatment targets.

BiomarkersPost-Exertional MalaiseImmune Dysregulation

Precision Medicine Study of Post-Exertional Malaise Epigenetic Changes in Myalgic Encephalomyelitis/Chronic Fatigue Patients During Exercise.

Sharma, Sayan, Hodges, Lynette D, Peppercorn, Katie et al.·International journal of molecular sciences·2025

This study looked at how exercise affects the chemical switches on our genes (epigenetics) in ME/CFS patients, particularly during post-exertional malaise (PEM)—the exhaustion that worsens after physical activity. Researchers took blood samples from five ME/CFS patients before, immediately after, and 24-48 hours after an exercise test, and found distinct patterns of genetic changes that were specific to ME/CFS patients and not seen in healthy controls. These changes affected genes related to immune function, inflammation, and blood vessel health, suggesting the body's response to exercise in ME/CFS is fundamentally different at the molecular level.

E3 PreliminaryPEM ✗PreliminaryReviewed

Profiling Antibody Reactivity to Gut Microbes in ME/CFS Patients.

Seton, Katharine A, Carding, Simon R·Methods in molecular biology (Clifton, N.J.)·2025

This study looks at how the immune system of ME/CFS patients reacts to bacteria in the gut. Many ME/CFS patients have changes in their gut bacteria and a leaky gut lining that allows bacteria and their toxic products to enter the bloodstream, potentially triggering widespread inflammation. The researchers developed methods to measure specific immune proteins (antibodies) that ME/CFS patients produce in response to these gut bacteria, compared to healthy household members.

Immune DysregulationGut Microbiome

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[Immunopathogenesis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)].

Yamamura, Takashi, Ono, Hirohiko, Sato, Wakiro·Brain and nerve = Shinkei kenkyu no shinpo·2018

This study found that people with ME/CFS have unusual patterns of immune system chemicals (cytokines) in their blood and spinal fluid, and some patients have antibodies that attack their own bodies. When researchers treated some ME/CFS patients with a medication that removes certain immune cells called B cells, patients improved. This suggests that ME/CFS may be caused by the immune system mistakenly attacking the body.

NeuroinflammationImmune Dysregulation

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Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Efficacy of Repeat Immunoadsorption.

Tölle, Markus, Freitag, Helma, Antelmann, Michaela et al.·Journal of clinical medicine·2020

This study tested a blood-cleaning treatment called immunoadsorption (IA) on five ME/CFS patients who had previously improved with this therapy. About two years later, they received the treatment again using a slightly modified approach. Four of the five patients showed improvement in their symptoms that lasted 6-12 months, and the treatment was well tolerated with no serious side effects.

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Infection Elicited Autoimmunity and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: An Explanatory Model.

Blomberg, Jonas, Gottfries, Carl-Gerhard, Elfaitouri, Amal et al.·Frontiers in immunology·2018

This study proposes that ME/CFS may develop when a person's immune system mistakenly attacks their own body after an infection, particularly affecting energy production in muscles and the brain. The researchers suggest that some people may have a genetic tendency to develop these harmful immune responses, especially when their gut bacteria are out of balance. When exposed to a triggering infection, the immune system can begin attacking proteins involved in energy metabolism and nerve function, leading to the exhaustion and post-exertion symptoms that characterize ME/CFS.

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Early Growth Response Gene Upregulation in Epstein-Barr Virus (EBV)-Associated Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Kerr, Jonathan·Biomolecules·2020

This study looked at specific genes called EGR genes that turn on in response to stress and infection. Researchers found that these genes were abnormally active in blood samples from some ME/CFS patients, and this activity matched up with signs of Epstein-Barr virus (EBV) reactivation. This suggests that in some people with ME/CFS, a dormant virus may be waking up and triggering an ongoing immune response.