Muscle-specific kinase (MuSK) antibody is found in a subset of patients with myasthenia gravis, primarily those seronegative for muscle acetylcholine receptor (AChR) antibodies. Decreasing antibody levels may be associated with the therapeutic response; therefore, clinical correlation must be strongly considered. A negative test result does not rule out a diagnosis of myasthenia gravis.
Antibodies to rat muscle-specific kinase, MuSK, have recently been identified in some generalized “seronegative” myasthenia gravis (SNMG) patients, who are often females with marked bulbar symptoms. Using immunoprecipitation of (125)I-labelled-human MuSK, 27 of 66 (41%) seronegative patients were positive, but 18 ocular SNMG patients, 105 AChR antibody-positive MG patients, and 108 controls were negative.
The antibodies are of high affinity (Kds around 100 pm) with titers between 1 and 200 nM. They bind to the extracellular Ig-like domains of soluble or native MuSK. Surprisingly they are predominantly in the IgG4 subclass. MuSK-antibody-associated MG may be different in etiological and pathological mechanisms.
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