Evidence browser

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome as a Hyper-Regulated Immune System Driven by an Interplay Between Regulatory T Cells and Chronic Human Herpesvirus Infections.

Sepúlveda, Nuno, Carneiro, Jorge, Lacerda, Eliana et al.·Frontiers in immunology·2019

This study suggests that ME/CFS may develop when the body's immune system becomes overprotective in response to common viruses like EBV, HSV-1, or HHV-6. Normally, the immune system fights off infections and then settles down, but in ME/CFS patients, special immune cells called Tregs may keep the immune system in a constant state of alert. Using computer models, researchers showed how this could lead to ongoing inflammation and fatigue.

E3 PreliminaryMechanismPEM not requiredObservational

Network structure underpinning (dys)homeostasis in chronic fatigue syndrome; Preliminary findings.

Clark, James E, Ng, Wan-Fai, Rushton, Stephen et al.·PloS one·2019

This study looked at how three key body systems (nervous system, stress hormone system, and immune system) work together in ME/CFS patients compared to healthy people. Researchers measured blood pressure, heart rate, and stress hormones at rest, then used a special mathematical approach to map how these measurements connect to each other. They found that in ME/CFS patients, these connections form a different pattern than in healthy controls, with a few key measurements being especially influential.

E3 PreliminaryMechanismPEM unclearObservational

Epstein-Barr Virus Induced Gene-2 Upregulation Identifies a Particular Subtype of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis.

Kerr, Jonathan R·Frontiers in pediatrics·2019

This study found that about 38-55% of ME/CFS patients have higher levels of a specific gene called EBI2 turned on in their immune cells. Patients with this EBI2 pattern appear to have more severe symptoms and different antibody levels compared to other ME/CFS patients. Because EBI2 is known to affect both immune function and brain function, finding this subtype could help explain why ME/CFS patients experience such different symptoms and may lead to new treatments.

BiomarkersImmune System

E3 PreliminaryMechanismPEM unclearCross-Sectional

Genetic Predisposition for Immune System, Hormone, and Metabolic Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Pilot Study.

Perez, Melanie, Jaundoo, Rajeev, Hilton, Kelly et al.·Frontiers in pediatrics·2019

Researchers analyzed the DNA of 383 ME/CFS patients to look for genetic variations that might make someone more susceptible to developing the illness. They found thousands of genetic differences that were more common in ME/CFS patients compared to the general population, and these differences clustered in three main areas: immune system function, hormone regulation, and metabolism. While this suggests genetics may play a role in ME/CFS vulnerability, it doesn't explain the entire cause of the disease.

Energy MetabolismImmune System

Transient receptor potential melastatin 2 channels are overexpressed in myalgic encephalomyelitis/chronic fatigue syndrome patients.

Balinas, Cassandra, Cabanas, Helene, Staines, Donald et al.·Journal of translational medicine·2019

This study looked at immune cells called NK cells in people with ME/CFS, focusing on special channels on their surface called TRPM2 that control calcium flow. Researchers found that ME/CFS patients had higher levels of these TRPM2 channels compared to healthy people, and their NK cells were less effective at fighting infections. When researchers tried two different drugs to modify these channels, the drugs reduced TRPM2 levels but did not improve the cells' ability to fight infections.

Epstein-Barr virus (EBV) reactivation and therapeutic inhibitors.

Kerr, Jonathan R·Journal of clinical pathology·2019

This review examines how Epstein-Barr virus (EBV), a common virus that most people catch at some point in their lives, can become active again in the body—especially during stress—and may contribute to ME/CFS and other illnesses. The authors discuss ways to test for active EBV and review existing medications and supplements that might help prevent the virus from reactivating.

Neuroimmunology: What Role for Autoimmunity, Neuroinflammation, and Small Fiber Neuropathy in Fibromyalgia, Chronic Fatigue Syndrome, and Adverse Events after Human Papillomavirus Vaccination?

Ryabkova, Varvara A, Churilov, Leonid P, Shoenfeld, Yehuda·International journal of molecular sciences·2019

This review explores three interconnected biological processes that may cause fibromyalgia and chronic fatigue syndrome (ME/CFS): the immune system attacking the body's own tissues, inflammation in the nervous system, and damage to small nerve fibers. The authors propose that these three mechanisms work together and may explain why patients experience widespread pain, extreme fatigue, and other symptoms like brain fog and sleep problems. They also examine whether similar mechanisms might explain some adverse reactions to HPV vaccination.

Myalgia and chronic fatigue syndrome following immunization: macrophagic myofasciitis and animal studies support linkage to aluminum adjuvant persistency and diffusion in the immune system.

Gherardi, Romain K, Crépeaux, Guillemette, Authier, François-Jérome·Autoimmunity reviews·2019

This review examines whether ME/CFS could be triggered by aluminum-containing substances in certain vaccines. The authors present evidence that aluminum particles may persist in immune cells and travel to the brain, potentially causing the cognitive problems, muscle pain, and fatigue seen in ME/CFS. They argue this condition represents a broader category of vaccine-related adverse effects called ASIA.

E3 PreliminaryReviewPEM not requiredReview-Narrative

Chronic fatigue syndrome (CFS): Suggestions for a nutritional treatment in the therapeutic approach.

Bjørklund, Geir, Dadar, Maryam, Pen, Joeri J et al.·Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie·2019

This review article examines how nutrition might play a role in chronic fatigue syndrome (CFS). The authors found that people with CFS often have low levels of certain vitamins and minerals—like vitamin C, B vitamins, magnesium, zinc, and others—and that these deficiencies may make CFS symptoms worse. The review suggests that nutritional support could be an important part of treating CFS alongside other medical approaches.

Myalgic encephalomyelitis or chronic fatigue syndrome: how could the illness develop?

Morris, Gerwyn, Maes, Michael, Berk, Michael et al.·Metabolic brain disease·2019

This study proposes a theory for how ME/CFS might develop, starting with an infection that triggers lasting problems in the body's immune system and stress response. The authors suggest that in genetically vulnerable people, this leads to a chain of events: increased inflammation, intestinal problems that allow bacteria-related substances to enter the bloodstream, nervous system dysfunction, and eventually a state where the immune system becomes exhausted and less able to fight back. This model tries to explain why ME/CFS patients have the specific symptoms and lab abnormalities doctors observe.

E3 PreliminaryReviewPEM requiredReview-Narrative

Understanding Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and the Emerging Osteopathic Approach: A Narrative Review.

Larrimore, Christopher, Ramnot, Amanda, Jaghab, Annmarie et al.·The Journal of the American Osteopathic Association·2019

This article reviews what scientists know about ME/CFS, including its symptoms, how it affects the body, and why it's hard to diagnose. The authors discuss both traditional medical approaches and osteopathic treatment (a type of hands-on therapy that focuses on the body's structure and function) as possible ways to help people with ME/CFS feel better. The review emphasizes that ME/CFS is a real, serious illness that deserves more awareness among doctors and better treatment options.

Immune SystemCognitive ImpairmentPost-Exertional Malaise

E3 PreliminaryCohortPEM unclearObservational

HERV-K and HERV-W transcriptional activity in myalgic encephalomyelitis/chronic fatigue syndrome.

Rodrigues, Lucas S, da Silva Nali, Luiz H, Leal, Cibele O D et al.·Auto- immunity highlights·2019

This study looked at whether certain viral fragments called HERV-K and HERV-W were more active in the blood of ME/CFS patients. Researchers found that HERV-K was elevated in people with moderate ME/CFS but not in those with severe disease, while HERV-W showed no difference. These findings suggest that viral elements may play a role in ME/CFS, though much more research is needed to understand what this means.

Validation of impaired Transient Receptor Potential Melastatin 3 ion channel activity in natural killer cells from Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis patients.

Cabanas, H, Muraki, K, Balinas, C et al.·Molecular medicine (Cambridge, Mass.)·2019

This study looked at a specific type of protein channel (called TRPM3) found on immune cells called natural killer cells in ME/CFS patients. The researchers used specialized equipment to measure how these channels function and found they work differently in ME/CFS patients compared to healthy people. This difference could help explain why immune function is impaired in ME/CFS and might point toward new treatment options.

Epstein-Barr Virus dUTPase Induces Neuroinflammatory Mediators: Implications for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Williams PhD, Marshall V, Cox, Brandon, Lafuse PhD, William P et al.·Clinical therapeutics·2019

This study explores whether a protein from the Epstein-Barr virus (EBV) may trigger brain inflammation in ME/CFS patients. Researchers found that this viral protein can change how brain cells function and alter important chemical pathways involved in energy, mood, and pain processing. The findings suggest that in some ME/CFS patients, this viral protein might contribute to fatigue, pain, and thinking difficulties.

Naltrexone Restores Impaired Transient Receptor Potential Melastatin 3 Ion Channel Function in Natural Killer Cells From Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients.

Cabanas, Helene, Muraki, Katsuhiko, Staines, Donald et al.·Frontiers in immunology·2019

This study looked at a protein channel called TRPM3 in immune cells from ME/CFS patients and found it wasn't working properly. The researchers discovered that a drug called naltrexone (an opioid blocker used off-label for ME/CFS) could restore the function of this damaged channel in laboratory tests. This finding suggests naltrexone may help ME/CFS symptoms by fixing this broken immune mechanism.

E3 PreliminaryReviewPEM not requiredReview-Narrative

Oxidative stress in exercise training: the involvement of inflammation and peripheral signals.

Magherini, Francesca, Fiaschi, Tania, Marzocchini, Riccardo et al.·Free radical research·2019

When we exercise, our bodies produce harmful molecules called free radicals that can damage cells. While some free radicals are normal and needed for muscle function, too many can cause problems. This review explains how intense exercise, stress, and not eating enough can create excessive free radicals and inflammation, which might lead to chronic fatigue and overtraining syndrome—conditions where the body cannot recover properly from exercise.

Immune SystemPost-Exertional Malaise

E3 PreliminaryCommentaryPEM unclearEditorial

Recent advances in our understanding of mast cell activation - or should it be mast cell mediator disorders?

Theoharides, Theoharis C, Tsilioni, Irene, Ren, Huali·Expert review of clinical immunology·2019

Mast cells are immune cells in your body that release chemical messengers (mediators) in response to many different triggers—not just allergies. When these cells release too many mediators, they can cause widespread symptoms affecting multiple body systems, including the brain and nervous system. This review suggests that doctors should look for elevated levels of these chemical messengers to help diagnose and treat these conditions, rather than waiting for the traditional markers (like histamine and tryptase) that don't always show up.

Leveraging Prior Knowledge of Endocrine Immune Regulation in the Therapeutically Relevant Phenotyping of Women With Chronic Fatigue Syndrome.

Morris, Matthew C, Cooney, Katherine E, Sedghamiz, Hooman et al.·Clinical therapeutics·2019

This study used computer modeling to understand how hormones and immune system chemicals become unbalanced in ME/CFS. Researchers measured 17 immune markers in women with ME/CFS before, during, and after exercise, then created detailed mathematical models to predict what other hormones and chemicals might also be out of balance. The models suggested that two existing drugs (rintatolimod and rituximab) might help different subgroups of patients, depending on their specific hormone and immune profiles.