IgA autoantibodies demonstrate a novel mechanism of MuSK myasthenia gravis pathology

This cutting-edge article by Gianvito Masi et al. identifies a previously unrecognized pathogenic antibody isotype in a subset of patients with MuSK myasthenia gravis (MuSK MG): MuSK-specific IgA coexists with IgG4 and can modulate pathogenesis both independently and in cooperation with MuSK IgG4. Patient-derived MuSK IgA monoclonal antibodies demonstrate partial Musk agonism and potential antagonism of MuSK IgG4; MuSK-specific IgA-IgG combination enhances clustering disruption, and MuSK-specific-IgA induces myasthenic phenotypes in murine models. These data suggest a mucosal/environmental contribution to disease and highlight new avenues for targeted therapies and more sensitive diagnostic approaches.