Clinical pitfalls and serological diagnostics of MuSK myasthenia gravis
Young Nam Kwon, Mark Woodhall, Jung‐Joon Sung, Kwang‐Kuk Kim, Young‐Min Lim, Hyunjin Kim, Jee‐Eun Kim, Seol‐Hee Baek, Byung‐Jo Kim, Jin‐Sung Park, Hung Youl Seok, Dae‐Seong Kim, Ohyun Kwon, Kee Hong Park, Eunhee Sohn, Jong Seok Bae, Byung-Nam Yoon, Nam‐Hee Kim, Suk‐Won Ahn, Kyomin Choi, Jeeyoung Oh, Hyung Jun Park, Kyong Jin Shin, Sang-Gon Lee, Jinseok Park, Seung Hyun Kim, Jung Im Seok, Dae Woong Bae, Jae Young An, In Soo Joo, Seok Jin Choi, Tai‐Seung Nam, Sun‐Young Kim, Ki‐Jong Park, Ki-Han Kwon, Patrick Waters, Yoon‐Ho Hong
Abstract
BACKGROUND: We aimed to evaluate the diagnostic accuracy of enzyme-linked immunosorbent assay (ELISA) for anti-muscle specific tyrosine kinase (MuSK) antibody (Ab) in a large cohort of anti-acetylcholine receptor (AChR) Ab-negative generalized myasthenia gravis (MG), and also to investigate clinical contexts for the diagnosis of MuSK MG. METHODS: A retrospective study of 160 patients with a clinical suspicion of AChR Ab-negative generalized MG was performed. The serum samples were tested for anti-clustered AChR Ab by cell-based assay (CBA), anti-MuSK Ab by ELISA, CBA and/or radioimmunoprecipitation assay (RIPA). Clinical data were compared between anti-MuSK Ab-positive MG and double seronegative (AChR and MuSK) MG groups. RESULTS: After excluding non-MG and clustered AChR Ab-positive patients, we identified 89 patients as a cohort of AChR Ab-negative generalized MG. Anti-MuSK Ab was positive by ELISA in 22 (24.7%) patients. While CBA identified five additional anti-MuSK Ab-positive patients, the results of ELISA were mostly consistent with CBA and RIPA with Cohen's kappa of 0.80 and 0.90, respectively (p < 0.001). The most frequent differential diagnosis was motor neuron disease particularly of bulbar onset which showed remarkably overlapping clinical and electrophysiological features with MuSK MG at presentation. CONCLUSION: While confirming the highest sensitivity of CBA for detecting anti-MuSK Ab, our results highlight the clinical pitfalls in making a diagnosis of MuSK MG and may support a diagnostic utility of MuSK-ELISA in clinical practice.