Detection and characterization of MuSK antibodies in seronegative myasthenia gravis

TLDR

MuSK antibodies have been identified in a subset of seronegative myasthenia gravis patients, typically female with bulbar symptoms, suggesting a distinct etiological and pathological mechanism. In this study, 41 % of seronegative myasthenia gravis patients tested positive for high‑affinity MuSK antibodies, predominantly IgG4, that bind the extracellular Ig‑like domains of MuSK, whereas ocular SNMG patients, AChR‑positive MG patients, and controls were negative.

Abstract

Abstract 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 differnet in etiological and pathological mechanisms.