A potential biomarker for the efficacy of complement inhibitors in myasthenia gravis

Background In acetylcholine receptor (AChR) antibody–positive myasthenia gravis (MG), complement activation is a major mechanism underlying impaired neuromuscular transmission and complement inhibitors are used in clinical practice. In the absence of biomarkers predicting responsiveness to complement inhibitors, this study aimed to identify novel predictors. Methods Serum samples from 14 patients with AChR antibody–positive MG and 10 healthy controls (HCs) were incubated with AChR-expressing HEK293 cells. AChR binding IgG and membrane attack complex (MAC) deposition were quantified by flow cytometry. The correlation of these indices with clinical manifestations was analyzed. Results Patients with MG showed higher mean fluorescence intensity (MFI) than HCs for AChR-bound IgG (median: 4614 vs 172; 95% CI 1588–7451, P < 0.001) and MAC deposition (488 vs 227; 95% CI 59–495, P < 0.001). The MFI of AChR-bound IgG correlated with baseline MG Activities of Daily Living (MG-ADL) scores (Spearman r s = 0.58; 95% CI 0.05–0.85, P = 0.033). Improvement in MG-ADL scores correlated with the MFI of AChR-bound IgG, MAC deposition, and the proportion of AChR-bound IgG + /MAC deposition + double-positive cells. Responders to complement inhibitors had higher proportions of double-positive cells than non-responders (median: 74% vs 0%; 95% CI 15–94, P = 0.022). The MFI values of AChR-bound IgG correlated with disease severity, and the proportion of double-positive cells may represent a potential biomarker of therapeutic response to complement inhibition. Prospective validation is needed to assess its predictive value.