Advances in B Cell Targeting for Treating Muscle-Specific Tyrosine Kinase-Associated Myasthenia Gravis.

Abstract

Myasthenia gravis (MG) is a typical autoimmune disease of the nervous system. It is characterized by skeletal muscle weakness and fatigue due to impaired neuromuscular junction transmission mediated by IgG autoantibodies. Muscle-specific receptor tyrosine kinase-associated MG (MuSK-MG), a rare and severe subtype of MG, is distinguished by the presence of anti-MuSK antibodies; it responds poorly to traditional therapies. Recent research on MuSK-MG treatment has focused on specific targeted therapies. Since B cells play a critical pathogenic role in producing autoantibodies and inflammatory mediators, they are often considered the preferred target for treating MuSK-MG. Currently, various B cell-targeted drugs have been developed to treat MuSK-MG; they have shown good therapeutic effects. This review explores the evolving landscape of B cell-targeted therapies in MuSK-MG, focusing on their mechanisms, efficacy, and safety, and the current limitations associated with their use. We discuss current B cell-targeted therapies aimed at depleting or modulating B cells via both direct and indirect approaches. Furthermore, we focus on novel and promising strategies such as Chimeric Autoantibody Receptor T cell therapy, which explicitly targets MuSK-specific B cells without compromising general humoral immunity. Finally, this review provides an outlook on the potential benefits and limitations of B cell-targeted therapy in developing new therapies for MuSK-MG. We conclude by discussing future research efforts needed to optimize these therapies, expand treatment options, and improve long-term outcomes in MuSK-MG management.