antiMuSK

Anti-MuSK antibodies are autoantibodies directed against muscle-specific kinase (MuSK), a receptor tyrosine kinase essential for the formation and maintenance of the postsynaptic apparatus at the neuromuscular junction. They occur in a subset of myasthenia gravis patients, particularly those who test negative for acetylcholine receptor (AChR) antibodies.

MuSK is part of the agrin-LRP4-MuSK signaling pathway that induces clustering of acetylcholine receptors at the motor endplate. Anti-MuSK antibodies are predominantly of the IgG4 subclass and interfere with MuSK signaling, disrupting AChR clustering rather than causing direct complement-mediated injury. This leads to impaired neuromuscular transmission.

Clinically, anti-MuSK myasthenia gravis often presents with prominent bulbar weakness (dysarthria, dysphagia), facial weakness, and neck or shoulder girdle weakness, with variable ocular involvement. Respiratory crisis can occur. Thymic pathology is less common than in AChR MG.

Diagnosis relies on serology for MuSK antibodies, typically by cell-based assays or immunoprecipitation. AChR antibodies are usually absent or low. Electrophysiology may show a decremental response on repetitive nerve stimulation and abnormal jitter on single-fiber EMG, though findings may be variable.

Management includes immunosuppressive therapy, with corticosteroids and rituximab showing particular effectiveness. Other immunosuppressants such as azathioprine may be used. Therapies for exacerbations include plasma exchange or intravenous immunoglobulin. Acetylcholinesterase inhibitors may be less effective and can worsen symptoms in some patients. Thymectomy is generally not beneficial.

MuSK MG accounts for a minority of MG cases and often affects younger women; prognosis has improved with modern immunotherapies, though disease course remains heterogeneous.