Krock 2023 — Anti-SGC IgG titer correlates with FM symptom severity
One-paragraph summary
The precursor paper to Seefried 2025 from the same Karolinska/Goebel collaboration. Demonstrates that anti-satellite-glial-cell IgG titer correlates with FM symptom severity — i.e., FM patients with higher antibody titers have more severe disease across measures of pain, fatigue, and functional impairment. Critically positions anti-SGC IgG titer as a continuous-variable biomarker rather than a binary positive/negative classifier. This is the load-bearing evidence for BASIS-FM's titer-stratified primary-endpoint design — if titer didn't correlate with severity, there'd be no rationale for using titer-change as the primary outcome of an interventional trial. The paper also represents the project's strongest existing evidence for the autoimmune subtype as a gradable phenotype rather than a categorical subgroup.
Claims as triples
- anti_SGC_IgG_titer — predicts → widespread_pain [evidence: titer-severity correlation; confidence: emerging]
- IgG_fm — modulates → widespread_pain [evidence: dose-response across titer range; confidence: emerging]
- fm_autoimmune — present_in → widespread_pain [evidence: severe-FM enrichment in IgG-positive subset; confidence: emerging]
Methods note
Cross-sectional FM cohort. Anti-SGC IgG quantified by immunocytochemistry on rodent DRG sections (the Krock-Kosek-Svensson protocol later used by Jakobsson 2026 and the BASIS-FM trial design). Symptom severity assessed by validated FM scales (likely FIQ-R and MPQ; full text needed to confirm).
Limitations
- Cross-sectional — temporal direction not established (does high titer cause severe FM, or does severe FM lead to higher titer through some feedback?).
- Karolinska-group analyses; conflict-of-interest considerations apply (BASIS-FM trial design notes this and proposes independent reference-lab assay for resolution).
- Titer cut-points may differ between institutions; primary citation needs full-text retrieval to confirm assay reproducibility.
Open questions raised
- Is the titer-severity correlation linear or threshold-based? Linear → titer reduction proportionally improves symptoms; threshold → BASIS-FM should sub-stratify above/below the threshold.
- Does titer change over time within individual patients track symptom flares (Daban 2026 trigger model)?
- Do the 9 binding clusters identified by Seefried 2025 differ in their titer-severity correlation strength?
Triangulation notes
- Foundational for BASIS-FM trial design. The trial's primary endpoint (within-patient anti-SGC IgG titer change) and stratification (titer-positive only) both rely on this paper's establishment that titer is clinically meaningful.
- Combined with Seefried 2025 (prevalence) and Hanani 2026 (multi-ganglia mechanism), the autoimmune subtype is now characterized at three orthogonal dimensions: prevalence (~37%), mechanism (multi-ganglia SGC activation), and clinical correlate (titer-severity).
- The Karolinska/Goebel publication lineage: Goebel 2021 (passive transfer) → Krock 2023 (titer-severity) → Jakobsson 2026 (BA correlation) → Seefried 2025 (cohort prevalence). This is now the cleanest single research thread in the project's evidence base.
Bridges
- B3 (CRPS ↔ FM via pathogenic IgG): similar titer-severity analyses in CRPS would test whether the autoimmune mechanism scales similarly across conditions.