Longitudinal MuSK antibody levels may correlate with disease severity in MuSK myasthenia gravis

BACKGROUND: In muscle-specific kinase antibody-positive myasthenia gravis (MuSK-MG), the clinical utility of MuSK antibody levels as a biomarker for disease severity is debated, with conflicting reports on its correlation with clinical status. This study aimed to clarify this association by applying a rigorous statistical model to a longitudinal dataset followed from an immunotherapy-naïve state. METHODS: We conducted a retrospective longitudinal study on 6 patients with MuSK-MG tracked from their treatment-naïve baseline. The primary analysis used 103 data points where MuSK antibody levels and MG activities of daily living (MG-ADL) scores were available. A secondary analysis used the subset of 81 data points where total immunoglobulin G (IgG) levels were also concurrently measured. Generalized linear mixed-effects models (GLMM) were used to assess the intrapatient correlation, adjusting for interpatient variability by including a random intercept for each subject. RESULTS: First, the GLMM analysis of 103 data points revealed a strong positive intrapatient correlation between MuSK antibody levels and MG-ADL scores (P < 0.001). Second, in the subset analysis (n = 81), MuSK antibody levels remained positively and specifically correlated with MG-ADL scores (P = 0.002), whereas total IgG levels showed no independent correlation (P = 0.61) when included in the same model. CONCLUSIONS: MuSK antibody level, unlike total IgG, is a specific and valuable biomarker for monitoring intrapatient disease activity and therapeutic response. These findings strongly support the utility of serial MuSK antibody monitoring within individual patients.