Autoantibodies in Myasthenia Gravis: Cluster Analysis, and Clinical Correlations

Xupeng Sun ¹ Meijie Qu ^1* Xi Rong ^1* Mingxing Lv ^1* Yunbin Zhao ^1* Yunjun Yan ² lin liu ^3* Na Sun ^2* Hua Yue ^1* Min Liu ^1*

• ¹ Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China
• ² Jinan Dian Medical Laboratory CO., LTD. Shandong, China, qingdao, China
• ³ Key Laboratory of Digital Technology in Medical Diagnostics of Zhejiang Provinces, Hangzhou, Jiangsu Province, China

Objective: This study aims to explore autoantibody clusters and their correlations with clinical features in 644 myasthenia gravis (MG) patients.Methods: Medical records of 664 MG patients were reviewed. Five autoantibodies (AChR, MuSK, titin, RyR and LRP4) were selected for cluster analysis. The various clinical manifestations were compared between clusters. Separate association analyses between individual autoantibodies and clinical manifestations as well as among different MGFA subtypes were also performed without prior clustering.Results: Two separate autoantibody clusters were identified, with significantly different clinical manifestations. Cluster 1 (485 patients) was characterized by higher proportions of RyR-, titin-, and AChR-, while cluster 2 (179 patients) had higher proportions of RyR+, titin+, and AChR+. Cluster 2 patients were older and had elevated QMG scores and odds of complications, particularly hypertension, diabetes, cardiovascular and cerebrovascular diseases, and eye conditions. Individual antibody analysis revealed male cases were more likely to be AChR+ and titin+, and older age was associated with AChR+, RyR+ and titin+. Among MGFA subtypes, significant differences were detected in AChR, MuSk, titin, complications, thymoma, and hypertension. As MG severity increased from type I to type V, AChR+, RyR+, and titin+ proportions peaked at stage IIa. MuSK+ patients were relatively rare and mostly present in the subtype b group. Type b patients had higher MuSk+ prevalence and increased cardiovascular and cerebrovascular disease incidence rates compared with type a cases.Overall, cluster 2 features were less favorable to patients. This study provides valuable insights into the clinical and autoantibody profiles of Chinese MG patients.