E0 ConsensusPreliminaryPEM unclearReview-NarrativePeer-reviewedMachine draft
Autoimmune autonomic nervous system imbalance and conditions: Chronic fatigue syndrome, fibromyalgia, silicone breast implants, COVID and post-COVID syndrome, sick building syndrome, post-orthostatic tachycardia syndrome, autoimmune diseases and autoimmune/inflammatory syndrome induced by adjuvants.
Malkova, A M, Shoenfeld, Y · Autoimmunity reviews · 2023 · DOI
Quick Summary
This review examined whether ME/CFS, fibromyalgia, and several other conditions share a common problem: the immune system mistakenly attacks nerve controls that regulate heart rate, blood pressure, and other automatic body functions. Researchers found that people with these conditions often have similar symptoms like fatigue, dizziness, and brain fog, and some have autoantibodies (immune proteins) that target nerve receptors. The authors propose this 'autonomic nervous system imbalance' could be a unifying mechanism explaining why these diverse conditions feel so similar.
Why It Matters
This work may help explain why ME/CFS patients experience such consistent dysautonomic symptoms despite different disease triggers. If autoimmune autonomic dysfunction is confirmed as a common mechanism, it could accelerate development of blood tests for diagnosis and guide therapeutic strategies targeting GPCR autoimmunity, potentially benefiting multiple conditions simultaneously.
Observed Findings
- Dysautonomic symptoms (severe fatigue, dizziness, brain fog, memory loss, dry mouth/eyes, tachycardia) are frequently reported across ME/CFS, fibromyalgia, PCS, POTS, and other listed conditions.
- Autoantibodies against GPCRs have been detected in some patients with post-COVID syndrome, silicone breast implant syndrome, and autoimmune diseases.
- Clinical symptom profiles overlap significantly across these diverse etiological groups.
- GPCR autoimmunity represents a potential common mechanism across conditions previously considered separate entities.
Inferred Conclusions
- Autoimmune autonomic nervous system imbalance may represent a unifying pathophysiological mechanism across ME/CFS, fibromyalgia, POTS, post-COVID syndrome, and related conditions.
- Detection of GPCR-targeting autoantibodies could provide a biomarker for diagnosing and stratifying these patients.
- Proposed diagnostic criteria for autoimmune autonomic imbalance warrant prospective clinical validation.
Remaining Questions
- Do GPCR autoantibodies appear in all ME/CFS patients, or only a subset, and do levels correlate with symptom severity?
- Are specific GPCR epitopes pathogenic, or is the imbalance between agonist and antagonist autoantibodies the key driver?
What This Study Does Not Prove
This review does not prove that GPCR autoimmunity causes ME/CFS or that all ME/CFS patients have this mechanism—it proposes a hypothesis based on published findings. The study is observational synthesis rather than controlled experimental evidence, and the proposed diagnostic criteria are not yet validated in prospective patient cohorts. Association of autoantibodies with disease does not establish causation.
Tags
Symptom:Cognitive DysfunctionOrthostatic IntoleranceFatigueSensory Sensitivity
Biomarker:Autoantibodies
Phenotype:Infection-TriggeredLong COVID Overlap
Method Flag:Weak Case DefinitionMixed Cohort
Metadata
- DOI
- 10.1016/j.autrev.2022.103230
- PMID
- 36347462
- Review status
- Machine draft
- Evidence level
- Established evidence from major reviews, guidelines, or evidence maps
- Last updated
- 8 April 2026
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
Spotted an error in this entry? Report it →