The Fusion Protein MuSK-Fc Functions as a Decoy to Block the Binding of Anti-MuSK Antibodies to MuSK.

Abstract

Muscle-specific tyrosine kinase antibody-positive myasthenia gravis (MuSKMG) is a rare subtype of MG that is often more refractory to immune treatment than acetylcholine receptor (AChR) antibody-positive MG. Therefore, novel therapeutic strategies are needed. We previously developed AChR-Fc, an Fc fusion protein that neutralises pathogenic autoantibodies and suppresses pathogenic B cells while preserving normal immunity, as a potential treatment for AChR antibody-positive MG. Subsequently, we conducted preliminary experiments on MuSK-Fc, a fusion protein targeting MuSKMG, using patient serum samples. This study examined whether MuSK-Fc binds to MuSK antibodies and inhibits MuSK antibody binding to MuSK. We found that MuSK-Fc specifically binds to MuSK antibodies and prevents their interaction with MuSK. These findings indicate that MuSK-Fc may neutralise pathogenic antibodies and suppress disease activity in MuSKMG.