MUSK Antibodies
Autoantibodies against the acetylcholine receptor (AChR) are present in 80 to 90 percent of patients with myasthenia gravis, while autoantibodies directed against the muscle-specific tyrosine kinase receptor (MuSK) are present in 1 to 10% of cases. Patients with AChR antibody positive myasthenia gravis do not have MuSK antibodies.
MuSK receptor resides on the postsynaptic membrane of neurons and mediates agrin-dependent AChR clustering which is important for maintenance of the neuromuscular junction and differentiation of nerve terminals. Autoantibody binding to MuSK receptor disrupts this pathway and interferes with neuromuscular transmission.
Patients with myasthenia gravis due to MUSK antibody have distinguishing features from patients with myasthenia gravis due to AChR antibody. Patients with MUSK antibody are more often female and have earlier onset of disease in the third or fourth decade. Ptosis and double vision are the most common manifestations in patients with acetylcholine receptor antibodies but are less common and milder in patients with MUSK antibodies. MUSK antibodies are more commonly associated with bulbar dysfunction, axial weakness, facial weakness, and respiratory distress (in 60%). Because of these symptoms, patients with MUSK antibodies more often require hospitalization. Patients who are AChR-Ab negative and MUSK antibody positive tend to have a much lower incidence of thymic hyperplasia and thymoma.
MUSK antibodies are generally not present in those with well-established ocular myasthenia gravis, but they have been detected in a few cases.
MUSK antibody testing can clarify the diagnosis of myasthenia in the appropriate clinical setting when patients test negative for AChR antibodies. However, the initial management of clinically apparent myasthenia should be the same for patients with or without AChR antibodies.
References
Lee I et al. Weak and Winded, New Engl J Med 2019;381:76-82.
Gilhus NE. Myasthenia gravis. N Engl J Med 2016;375:2570-2581.
Bartoccioni E, Scuderi F, Minicuci GM, Marino M, Ciaraffa F, Evoli A. Anti-MuSK antibodies: correlation with myasthenia gravis severity. Neurology 2006;67:505-507.
