Anti-muscle-specific kinase B cell receptor (anti-MuSK BCR)

The anti-muscle-specific kinase (MuSK) B cell receptor is a membrane-bound immunoglobulin expressed on the surface of pathogenic B cells in patients with MuSK-positive myasthenia gravis (MuSK-MG) (Oh et al., 2023, Nature Biotechnology). This receptor specifically recognizes the MuSK protein, a receptor tyrosine kinase crucial for the formation and maintenance of the neuromuscular junction (Ellebrecht et al., 2016, Science). Binding of the BCR to MuSK triggers B cell activation and the production of pathogenic IgG4 autoantibodies that interfere with MuSK's interaction with LRP4, leading to impaired neuromuscular transmission and clinical muscle weakness (Cabaletta Bio, 2024). In therapeutic development, this BCR is the specific target for Chimeric Autoantibody Receptor (CAAR) T-cell therapy, such as MuSK-CAART (ClinicalTrials.gov, NCT05455034). These engineered T-cells express the MuSK extracellular domain to selectively identify and destroy only the B cells expressing the anti-MuSK BCR, sparing the rest of the immune system (Oh et al., 2023, Nature Biotechnology). This precision approach aims to eliminate the source of autoantibodies while avoiding the broad immunosuppression associated with traditional treatments (Cabaletta Bio, 2024). Monitoring of anti-MuSK antibody titers and B cell populations serves as a key biomarker for treatment efficacy (ClinicalTrials.gov, NCT05455034). Potential safety concerns include cytokine release syndrome and neurotoxicity, which are common to T-cell therapies (Oh et al., 2023, Nature Biotechnology).

Other names

MuSK-specific B cell receptorMuSK-reactive B cell receptoranti-MuSK autoantibody receptor

Selective depletion of pathogenic B cells through Chimeric Autoantibody Receptor (CAAR) T-cell mediated cytotoxicity