Goebel 2021 — IgG transfer from FM patients reproduces pain and SFN in mice

One-paragraph summary

IgG purified from serum of fibromyalgia patients, when injected into mice, produced increased pain sensitivity (mechanical and thermal hypersensitivity), reduced grip strength and locomotion, and reduced intraepidermal nerve fiber density. IgG from healthy controls did not. Patient IgG bound satellite glia in mouse and human dorsal root ganglia. The work suggests at least a subset of FM is mediated by pathogenic autoantibodies — a mechanistically distinct etiology from the dominant central-sensitization model and one of the few existing leads with a plausible "cure" path (antigen identification → targeted depletion).

Claims as triples

• IgG_fm — causes → widespread_pain [evidence: behavioral assays in mice; confidence: emerging]
• IgG_fm — causes → small_fiber_neuropathy [evidence: IENFD reduction in mouse hind paw; confidence: emerging]
• IgG_fm — present_in → dorsal_root_ganglion [evidence: immunohistochemistry; confidence: emerging]
• satellite_glia — bridges → autoantibody_mediated_pain [evidence: IgG binding pattern; confidence: bridging]
• autoantibody_mediated_pain — present_in → fm_autoimmune [evidence: subset of patient sera produced phenotype; confidence: emerging]

Methods note

IgG purified from sera of 44 FM patients and 27 controls. Daily i.p. injection into mice over 14 days; behavioral phenotyping (von Frey, Hargreaves, grip strength, locomotion); IENFD via skin biopsy of mouse hind paw; immunohistochemistry on mouse and human DRG sections. Authors: Liverpool / Karolinska / UCL groups.

Limitations

• Mouse model imperfectly maps to human FM symptomatology (no fatigue, sleep, cognitive readouts).
• Antigen target on satellite glia not yet identified.
• Did not stratify which FM patients' IgG was most pathogenic — subtype mapping not done.
• Replication at scale is the most important open question.

Open questions raised

• What is the antigen? Identification would enable a diagnostic and possibly a target.
• Are antibody-positive FM patients clinically distinguishable from antibody-negative ones?
• Does plasma exchange or B-cell depletion produce clinical benefit in antibody-positive patients?
• Does this overlap with the post-COVID FM-like presentations (i.e., is the antigen shared)?

Triangulation notes

• Supports fm_autoimmune subtype as a credible hypothesis.
• Mechanistically links IgG_fm → small_fiber_neuropathy, providing a candidate cause for the SFN seen in 40–60% of FM patients (per Üçeyler / Caro lines of work, not yet ingested).
• Connects to the autoimmune-neuropathy literature (CIDP, autoimmune SFN) where similar passive-transfer evidence exists.

Bridges

• Long COVID / post-acute infection syndromes: similar autoantibody-mediated SFN reports in long COVID. See synthesis/bridges.md B1.
• CRPS: autoantibody passive-transfer evidence also exists in CRPS — Goebel's group has paired papers. See synthesis/bridges.md B3.