IgG Subclass ( IgG1 ‐4) and IgA Autoantibody Profiles Against Muscle‐Specific Kinase in a Greek Cohort

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INTRODUCTION/AIMS: Muscle-specific kinase myasthenia gravis (MuSK-MG) is an autoimmune neuromuscular disorder predominantly mediated by IgG4 autoantibodies disrupting MuSK signaling. The contribution of other isotypes remains incompletely defined. We characterized the serological profile of a Greek cohort of MuSK-MG patients. METHODS: Baseline (n = 140) and longitudinal (available n = 99) samples from 140 patients, positive for anti-MuSK by radioimmunoprecipitation (RIPA) were analyzed using a live cell-based assay (L-CBA) to detect total IgG, IgG1-4 subclasses, IgM, and IgA. Also, disease and healthy controls (n = 102) were included. Selected samples were additionally analyzed by flow cytometry. Clinical data were available for specific patients. RESULTS: Our analysis revealed 15 distinct immunoglobulin combinations and provided insights into the presence of IgA isotype. IgG4 was the most common subclass in 120/140 of patients, followed by IgG1 in 79/140, IgG3 in 59/140, and IgG2 in 42/140 patients, while IgM positivity was detected in selected patients. Anti-MuSK IgA(1) immunoreactivity was detected in 54/140 patients, frequently co-occurring with IgG, and in four patients at baseline with only-IgA positivity. IgA was detected both near disease onset and at later stages, and persisted over time in rituximab-treated patients. Controls tested largely negative for IgA, although low-intensity signals were observed in six samples and were considered non-specific. L-CBA detected anti-MuSK IgA more frequently than flow cytometry. DISCUSSION: Our findings expand the serology of MuSK-MG beyond IgG subclasses, identifying IgA as an additional component of the anti-MuSK response. These results enhance further investigation into the clinical significance, pathogenic potential, and treatment-associated fluctuations of anti-MuSK IgA antibodies.

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