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Goebel A, Krock E, Gentry C, et al. Passive transfer of fibromyalgia symptoms from patients to mice. J Clin Invest. 2021;131(13):e144201. PMID 34196305

One-paragraph summary

IgG was purified from patients with fibromyalgia syndrome (FMS) and from healthy control subjects and administered to mice, alongside IgG-depleted patient serum as an additional control. Mice treated with FMS IgG developed increased sensitivity to noxious mechanical and cold stimulation, reduced locomotor activity, reduced paw grip strength and loss of intraepidermal innervation; nociceptive fibres in skin–nerve preparations from these animals showed increased responsiveness to cold and mechanical stimulation. IgG-depleted patient serum and healthy-control IgG produced no effect. Patient IgG did not activate naive sensory neurons directly, but labelled satellite glial cells and neurons in vivo and in vitro, as well as myelinated fibre tracts and a small number of macrophages and endothelial cells in mouse dorsal root ganglia (DRG) — and no cells in the spinal cord. FMS IgG also bound human DRG. The authors concluded that FMS IgG produces sensory hypersensitivity by sensitizing peripheral nociceptive afferents, and suggested that therapies reducing patient IgG titres may be effective.

Key findings

  • Phenotype transfers with the IgG fraction and not with IgG-depleted serum — the classic passive-transfer criterion for an antibody-mediated disease.
  • Behavioural readouts: mechanical and cold hypersensitivity, reduced locomotion, reduced grip strength.
  • Peripheral electrophysiology: increased nociceptor responsiveness to cold and mechanical stimulation in skin–nerve preparations.
  • Loss of intraepidermal innervation in treated mice — offering a mechanism by which the small-fibre pathology reported in ~half of FM patients could be a consequence of a circulating factor rather than a primary lesion.
  • Target localization: satellite glial cells and neurons in DRG; binding to human DRG; no spinal cord binding — the mechanism is peripheral-ganglionic, not central.
  • Patient IgG does not directly activate naive neurons, implying an indirect (glial-mediated or sensitizing) mode of action.

Limitations

  • Mouse model of hypersensitivity, not of fibromyalgia. Fatigue, cognitive symptoms and emotional distress — core to the human syndrome — are not modelled.
  • The autoantigen is unidentified. Binding is characterized histologically; the molecular target remains unknown, so affinity-purified antibody could not be tested in place of bulk IgG.
  • Dose and time course (purified IgG given over days) bear an unknown relationship to endogenous titres over years of illness.
  • Replication is not independent. PubMed searching (August 2026) returns four FM passive-transfer papers, all sharing authors with this one: Berwick 2025 (PMID 40408228), Israel 2025 (PMID 40898777), Israel 2026 (PMID 41955337). The 2025 Berwick paper explicitly "validated FMS-IgG passive transfer" in male mice using pooled serum from 18 patients, but retains Goebel and Andersson as authors.
  • The associated clinical assay is not specific. Anti-satellite-glial-cell IgG reactivity was found in post-acute COVID-19 syndrome and in people recently recovered from COVID-19, yet pooled PACS IgG was inert on transfer (Berwick 2025, PMID 40408228) — reactivity and pathogenicity dissociate.
  • No controlled immunotherapy trial in FM has tested the therapeutic corollary.

Why it matters

This is the strongest single piece of evidence that fibromyalgia has a peripheral, antibody-mediated component, and it reframes several older observations at once: small-fibre loss becomes potentially downstream rather than primary; the dorsal root ganglion becomes a plausible site of action; and a testable therapeutic hypothesis (lower the IgG) follows directly. It is the paper that made "is fibromyalgia an autoimmune disease?" a serious published debate rather than a fringe question (Clauw & Sarzi-Puttini 2023, PMID 37634681). What it has not yet done is survive replication by a fully independent laboratory, name its antigen, or generate a positive controlled trial — which is why FM remains unclassified as autoimmune.

Cited by wiki pages

  • autoimmunity-and-inflammation
  • pathophysiology-peripheral