MuSK Autoantibodies in Myasthenia Gravis: Experience with >28,000 Specimens Tested in a Clinical Laboratory (P3.169)

OBJECTIVE: To examine the positive rate of autoantibodies against muscle-specific tyrosine kinase (MuSK), with and without prior acetylcholine receptor (AChR) testing, in a clinical laboratory. BACKGROUND: Although most patients with generalized myasthenia gravis (MG) have antibodies against AChR, 10[percnt] to 15[percnt] of are seronegative for AChR. Within this group, about 40[percnt] have anti-MuSK antibodies (5[percnt] of the total MG population). Compared to AChR antibody-positive MG, MuSK antibody-positive MG typically exhibits a more rapidly progressive, severe disease course that often leads to a myasthenic crisis. Standard therapies, such as acetylcholinesterase-inhibitors and thymectomy, are often ineffective. DESIGN/METHODS: The frequency of MuSK autoantibodies was determined using de-identified test results from unique specimens (n=26,994 tested for MuSK, and n=1,151 for both AChR and MuSK analysis) reported by a clinical diagnostic laboratory. The patient population included 59[percnt] females and 41[percnt] males. RESULTS: The positive rate was 1.6 [percnt] (n=428 borderline and positive cases), with a predominance of females [83[percnt] female; mean age (MA) = 42 y; 17[percnt] male, MA = 50 y], respectively) in the group tested for MuSK alone. The median MuSK titer for both males and females was 1:2560. In the group tested seronegative for anti-AChR followed by MuSK, 1.7[percnt] (n=19) were MuSK-positive. The majority of these patients (n=18) were females (MA = 51 y). CONCLUSIONS: The predominance of young females and the mean age of AChR-seronegative individuals with MuSK-positive results are in agreement with other reports. This large study of more than 28,000 specimens referred to a clinical laboratory for MG serologic evaluation shows that the MuSK positive rate (1.6[percnt] to 1.7[percnt]) was significantly less than previously published results (5[percnt]). Study Supported by: Quest Diagnostics Disclosure: Dr. Goldberger has received personal compensation for activities with Quest Diagnostics. Dr. Sansoucy has received personal compensation for activities with Quest Diagnostics. Dr. Morneau has received personal compensation for activities with Quest Diagnostics. Dr. Burnham has received personal compensation for activities with Quest Diagnostics. Dr. Batish has received personal compensation for activities with Quest Diagnostics. Dr. Suer has received personal compensation for activities with Quest Diagnostics. Dr. Wang has received personal compensation for activities with Quest Diagnostics. Dr. Jaremko has received personal compensation for activities with Quest Diagnostics. Dr. Higgins has received personal compensation for activities with Quest Diagnostics.