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

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.

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.

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.

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.