[Immunopathogenesis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)].
Yamamura, Takashi, Ono, Hirohiko, Sato, Wakiro · Brain and nerve = Shinkei kenkyu no shinpo · 2018 · DOI
Quick Summary
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.
Why It Matters
This work supports the emerging understanding that ME/CFS has a biological, immune-mediated basis rather than a purely psychological etiology—an important validation for patients. The demonstration that a targeted immunological treatment (rituximab) shows efficacy provides a proof-of-concept for disease-modifying therapies and opens new avenues for clinical trials.
Observed Findings
- Elevated inflammatory and anti-inflammatory cytokines present in sera and cerebrospinal fluid of ME/CFS patients
- Presence of autoantibodies detected in subgroups of ME/CFS patients
- Clinical improvement observed in ME/CFS patients treated with anti-CD20 antibody (rituximab) in investigator-initiated trials
- Differences in immune markers between patient subgroups suggest heterogeneous immune phenotypes
Inferred Conclusions
- Immune abnormalities, particularly enhanced autoimmune responses, play a significant role in ME/CFS neuroinflammation
- B cells and their products (autoantibodies) may represent therapeutic targets in ME/CFS
- ME/CFS demonstrates features consistent with autoimmune and/or neuroimmunological disease pathogenesis
Remaining Questions
- Which specific autoantibodies are pathogenic in ME/CFS and what are their target antigens?
- Why do only subgroups of ME/CFS patients exhibit detectable autoimmune markers, and are there distinct disease subtypes?
- What is the mechanism by which B cell depletion alleviates symptoms—antibody reduction, altered cytokine production, or changes in B cell signaling?
- Are elevated cytokines in cerebrospinal fluid produced locally by CNS-resident immune cells or derived from peripheral circulation?
What This Study Does Not Prove
This study does not establish that autoimmunity is the primary cause of ME/CFS in all patients, as autoimmune markers are found only in subgroups. It does not prove that cytokine elevation is pathogenic rather than a consequence of disease, nor does it clarify whether B cell depletion works through reducing autoantibodies specifically or through other immune mechanisms.
Topics
Tags
Metadata
- DOI
- 10.11477/mf.1416200947
- PMID
- 29348373
- Review status
- Machine draft
- Evidence level
- Early hypothesis, preprint, editorial, or weak support
- Last updated
- 7 April 2026