Goebel 2025 — FM as an autoimmune condition (consolidation review)

One-paragraph summary

Author-led 2025 consolidation review by Goebel arguing that since the 2021 passive-transfer paper (Goebel et al, JCI), causative involvement of IgG-mediated autoimmunity in severe fibromyalgia syndrome has been demonstrated in passive-transfer paradigms across three independent patient cohorts (UK, Swedish, Canadian). The review argues the majority — possibly all — patients with severe FM harbor proalgetic serum-IgG autoantibodies, and frames the central next step as clinical-trial confirmation. An FcRn-directed therapeutic trial completed recruitment late 2023 with results expected late 2025.

Claims as triples

• IgG_fm — causes → widespread_pain [evidence: passive transfer in 3 cohorts; confidence: emerging]
• IgG_fm — causes → small_fiber_neuropathy [evidence: same; confidence: emerging]
• autoantibody_mediated_pain — present_in → fm_autoimmune [evidence: ~all severe FM patients harbor proalgetic IgG; confidence: emerging]
• fm_autoimmune — responds_to → ivig [evidence: hypothetical; FcRn trial pending; confidence: bridging]

Methods note

Author-led narrative review by Andreas Goebel (Liverpool), the original passive-transfer investigator. Reviews the 2021 JCI paper plus subsequent independent replications. Not a systematic review.

Limitations

• Author-led review by an originator of the autoimmune hypothesis — not an independent assessment.
• Cohort heterogeneity across the three replication sites (UK / Swedish / Canadian) is not fully harmonized.
• Antigen target is still unidentified — a fundamental gap that the review acknowledges.
• "Proalgetic IgG in majority/all of severe FM" is an aggressive claim that requires the standard caveat: severe-FM cohorts are selected, and the prevalence may not generalize to the full FM population.

Open questions raised

• What is the antigen? Identification is the bottleneck for diagnostic + targeted-therapy development. (Tracked as Q1.)
• Does FcRn inhibition (the trial that completed late-2023) actually benefit antibody-positive FM patients? (Tracked as Q8.)
• Is "anti-SGC IgG positive" a stable trait or does it fluctuate with FM disease activity?
• Does the autoimmune-FM cohort overlap with the post-COVID-FM cohort? (Tracked as Q7.)

Triangulation notes

• This review is the anchor for fm_autoimmune as an emerging-tier subtype. Combined with Seefried 2025 (replication, 184-sera cohort) and Hanani 2026 (multi-ganglia mechanism), it forms the strongest single thread in the project's current evidence base.
• Connects to bridge B3 (CRPS ↔ FM via pathogenic IgG): same lab, same paradigm, parallel evidence in CRPS predates the FM work.
• Connects to bridge B1 (long COVID ↔ FM via autoantibody-mediated SFN): if the antigen is shared, post-COVID FM may be a special case.

Bridges

• B1 (Long COVID ↔ FM via autoantibody-mediated SFN) — strengthened.
• B3 (CRPS ↔ FM via pathogenic IgG) — strengthened; this review explicitly draws the analogy to CRPS literature.