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

Sotzny, Franziska, Blanco, Julià, Capelli, Enrica et al. · Autoimmunity reviews · 2018 · DOI

Quick Summary

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.

Why It Matters

This review consolidates growing evidence that autoimmunity plays a significant role in at least some ME/CFS cases, moving the field beyond purely infectious or behavioral explanations. The clinical response to B-cell depleting therapy provides tangible proof-of-concept that immune-targeted interventions can benefit ME/CFS patients, potentially opening pathways to more effective, mechanism-based treatments.

Observed Findings

Immune dysregulation documented in ME/CFS including abnormal cytokine profiles and immunoglobulin levels
Reduced natural killer cell cytotoxicity in ME/CFS patients
Identification of autoantibodies against neurotransmitter receptors in ME/CFS individuals
B-cell depletion with rituximab produced clinical benefits in approximately 50% of ME/CFS patients in Norwegian trials
Evidence for severe metabolic disturbances potentially mediated by serum autoantibodies

Inferred Conclusions

At least a subset of ME/CFS patients has autoimmune etiology, distinct from other disease mechanisms
Autoantibodies, particularly those targeting neurotransmitter receptors, likely contribute to ME/CFS pathophysiology
B-cell targeting therapy may be a viable treatment approach for autoimmune-mediated ME/CFS
Further characterization of autoantibodies and their role in disease onset is essential for improving diagnosis and treatment strategies

Remaining Questions

Which patient characteristics or biomarkers identify those with autoimmune-mediated ME/CFS versus other disease mechanisms?
What are the specific autoantigen targets and how do they contribute to neurological and metabolic symptoms?
Why do only approximately 50% of patients respond to rituximab, and can treatment be optimized for broader efficacy?
How do autoimmune mechanisms interact with other proposed pathogenic factors (viral, mitochondrial, metabolic) in ME/CFS?

What This Study Does Not Prove

This review does not establish that autoimmunity causes ME/CFS in all patients—it identifies autoimmune mechanisms in a subset. The review does not prove causation from correlational immunological findings, nor does it explain why only some patients respond to rituximab or identify which patient characteristics predict autoimmune versus other disease mechanisms. Long-term treatment efficacy and optimal patient selection criteria remain unresolved.

Topics

Metabolic Dysfunction Immune Dysregulation

Metadata

DOI: 10.1016/j.autrev.2018.01.009
PMID: 29635081
Review status: Editor reviewed
Evidence level: Established evidence from major reviews, guidelines, or evidence maps
Last updated: 7 April 2026