ImmunologyPEM-relevant

Immune System

1194 studies in the atlas

Immune system abnormalities are among the most frequently reported findings in ME/CFS research. Documented changes include altered cytokine profiles, reduced natural killer cell function, and signs of chronic immune activation. The consistency of these findings across studies suggests immune involvement, though the precise role — whether causal, contributory, or secondary — remains unclear.

What we know

Reduced natural killer (NK) cell cytotoxicity has been reported across multiple independent studies and is one of the more replicated immune findings
Altered cytokine profiles have been documented in several studies, though results vary by cohort, disease duration, and methodology
Signs of chronic immune activation are present in a subset of patients
Overlap in immune signatures between ME/CFS and Long COVID has been observed in recent comparative studies

What remains uncertain

Autoimmune mechanisms may be involved in some patients — autoantibodies against adrenergic and muscarinic receptors have been detected in small studies, but replication is limited
Viral persistence or reactivation (particularly EBV) may maintain chronic immune activation in some individuals
Immune cell metabolic dysfunction may overlap with the broader metabolic abnormalities observed in ME/CFS
Mast cell activation has been reported in a subset of patients, but its prevalence and significance are not well established
Gut microbiome changes may influence immune function, though causal evidence in ME/CFS is early

What is emerging

Whether immune subtypes exist that predict disease course or treatment response
The precise boundary between autoimmune involvement and immune exhaustion
Whether immunomodulatory treatments benefit specific patient subgroups (trials of rituximab and IVIG have produced mixed results)
How infection-triggered onset relates mechanistically to ongoing immune-system changes
Whether any immune marker is reliable enough to serve as a diagnostic biomarker

Start here

E0 ConsensusPEM required

Biomarkers for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a systematic review.

Maksoud, Rebekah, Magawa, Chandi, Eaton-Fitch, Natalie et al.·BMC medicine·2023

Researchers reviewed 101 studies looking for biological markers (biomarkers) that could help diagnose ME/CFS. A biomarker is something measurable in your blood or body that shows a disease is present. While scientists found many potential biomarkers affecting the immune system, energy production, circulation, and other body functions, none have been proven reliable enough to use as a diagnostic test yet.

Research Momentum

1186 publications over 40 years. Recent trend: steady (57/year over the last 3 years).

Top Studies

60 of 1194, sorted by evidence level and year

E0ReviewPEM ✓

Insights into the Complex Biological Network Underlying Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

2025

Dudova, Dobrina et al.·International journal of molecular sciences·Review-Narrative

E0ReviewPEM ✓

Unravelling the Connection Between Energy Metabolism and Immune Senescence/Exhaustion in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

2025

Van Campenhout, Jente et al.·Biomolecules·Review-Narrative

Immune System

What we know

What remains uncertain

What is emerging

Biomarkers for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a systematic review.

Research Momentum

Top Studies

Insights into the Complex Biological Network Underlying Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Unravelling the Connection Between Energy Metabolism and Immune Senescence/Exhaustion in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Cognitive Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-Aetiology and Potential Treatments.

Gut Microbiome and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Insights into Disease Mechanisms.

The microbiota-gut-brain axis in myalgic encephalomyelitis/chronic fatigue syndrome: a narrative review of an emerging field.

From tradition to healing: the promise of acupuncture in managing chronic fatigue syndrome.

Microglia and Sleep Disorders.

Meta-analysis of natural killer cell cytotoxicity in myalgic encephalomyelitis/chronic fatigue syndrome.

Autoimmunity's enigmatic role: exploring the connection with myalgic encephalomyelitis/chronic fatigue syndrome.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: the biology of a neglected disease.

Chronic Fatigue Syndrome: Diagnosis, Treatment, and Future Direction.

Advancing Research and Treatment: An Overview of Clinical Trials in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Future Perspectives.

Research progress on pathogenesis of chronic fatigue syndrome and treatment of traditional Chinese and Western medicine.

Biomarkers for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a systematic review.

Surveying the Metabolic and Dysfunctional Profiles of T Cells and NK Cells in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Evaluation of viral infection as an etiology of ME/CFS: a systematic review and meta-analysis.

Therapeutic Implications of the Microbial Hypothesis of Mental Illness.

Animal Models for Neuroinflammation and Potential Treatment Methods.

Epstein-Barr Virus and the Origin of Myalgic Encephalomyelitis or Chronic Fatigue Syndrome.

Associations Between Psychological and Immunological Variables in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A Systematic Review.

The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in myalgic encephalomyelitis/chronic fatigue syndrome: A meta-analysis of public DNA methylation and gene expression data.

A Comprehensive Update of the Current Understanding of Chronic Fatigue Syndrome.

Back to the Future? Immunoglobulin Therapy for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

New Insights on the Role of TRP Channels in Calcium Signalling and Immunomodulation: Review of Pathways and Implications for Clinical Practice.

Pathomechanisms and possible interventions in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Human Herpesviruses Are Back!

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): Where will the drugs come from?

Environmental, Neuro-immune, and Neuro-oxidative Stress Interactions in Chronic Fatigue Syndrome.

Epigenetic Components of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Uncover Potential Transposable Element Activation.

A systematic review of natural killer cells profile and cytotoxic function in myalgic encephalomyelitis/chronic fatigue syndrome.

The clinical value of cytokines in chronic fatigue syndrome.

Inflammatory proteins are altered in chronic fatigue syndrome-A systematic review and meta-analysis.

A systematic review of cytokines in chronic fatigue syndrome/myalgic encephalomyelitis/systemic exertion intolerance disease (CFS/ME/SEID).

Pathological Mechanisms Underlying Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

[Myalgic encephalomyelitis or chronic fatigue syndrome].

Does the microbiome and virome contribute to myalgic encephalomyelitis/chronic fatigue syndrome?

Metabolic abnormalities in chronic fatigue syndrome/myalgic encephalomyelitis: a mini-review.

[Neurologic Abnormalities in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Review].

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Evidence for an autoimmune disease.

Nutritional modulation of the intestinal microbiota; future opportunities for the prevention and treatment of neuroimmune and neuroinflammatory disease.

Chronic fatigue syndrome and the immune system: Where are we now?

Hypothalamic-Pituitary-Adrenal Hypofunction in Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS) as a Consequence of Activated Immune-Inflammatory and Oxidative and Nitrosative Pathways.

A Role for the Intestinal Microbiota and Virome in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)?

Chronic fatigue syndrome and circulating cytokines: A systematic review.

Altered immune response to exercise in patients with chronic fatigue syndrome/myalgic encephalomyelitis: a systematic literature review.

The neuropsychiatric and neuropsychological features of chronic fatigue syndrome: revisiting the enigma.

Natural killer cells in patients with severe chronic fatigue syndrome.

Biomarkers for chronic fatigue.

Meta analysis of Chronic Fatigue Syndrome through integration of clinical, gene expression, SNP and proteomic data.

Neuroaetiology of chronic fatigue syndrome: an overview.

[Viral infections in chronic fatigue syndrome].

[Chronic fatigue syndrome: biochemical examination of blood].

Chronic fatigue syndrome: an update focusing on phenomenology and pathophysiology.

A systematic review and critical evaluation of the immunology of chronic fatigue syndrome.

Chronic fatigue syndrome: reviewing the research findings.

Chronic fatigue syndrome: an immunological perspective.

Chronic fatigue syndrome. 1: Etiology and pathogenesis.

Clinical correlates of infection with human herpesvirus-6.

Pathogenic tracks in fatigue syndromes.

Studies of herpesvirus infection in chronic fatigue syndrome.