Dataset Information

Autoantibodies in myasthenia gravis: cluster analysis and clinical correlations.

ABSTRACT:

Objective

This study aimed 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 that 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 types I to 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 than type a cases.

Conclusion

Overall, cluster 2 features were less favorable to patients. This study provides valuable insights into the clinical and autoantibody profiles of Chinese MG patients.

SUBMITTER: Sun X

PROVIDER: S-EPMC11834866 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature

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Publications

Autoantibodies in myasthenia gravis: cluster analysis and clinical correlations.

Sun Xupeng X Qu Meijie M Rong Xi X Lv Mingxing M Zhao Yunbin Y Yan Yunjun Y Liu Lin L Sun Na N Yue Hua H Liu Min M

Frontiers in neurology 20250204

<h4>Objective</h4>This study aimed to explore autoantibody clusters and their correlations with clinical features in 644 myasthenia gravis (MG) patients.<h4>Methods</h4>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 MGF ...[more]

PMID: 39968461

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Project description:Myasthenia gravis (MG) is an autoimmune disease affecting the neuromuscular junction, whose clinical hallmark is muscle weakness and early fatigability. Azathioprine (AZA) is commonly used in Myasthenia Gravis therapy. AZA is a purine antagonist, which inhibits the cell cycle in the resting and DNA synthesis phases. It is usually used as an immunosuppressant to block T- and B-cell proliferation. AZA, bioconverted to 6-mercaptopurine by glutathione S-transferase (GST), can be metabolized either through the hypoxanthine phosphoribosyl transferase pathway to active 6-thioguanine nucleotides (6-TGN) or through the thiopurine S-methyltransferase (TPMT) pathway to inactive methyl-thiopurine metabolites. The incorporation of active 6-TGNs into DNA, causing breaks in DNA strands resulting in interference with RNA production and thereby protein synthesis, is responsible for the drug effect. The response to AZA is determined by which metabolic pathway is being favored. While balanced use of both HPRT and TPMT pathways results in responsiveness to AZA, hyperactivity of TPMT skews the balance towards the TPMT pathway and results in unresponsiveness to AZA with no pharmacological effect. In contrast, low TPMT activity skews the balance towards the HPRT pathway, resulting in increasing side-effects due to the accumulation of 6-TGNs. Current treatments for MG therapy are often inadequate because less than 40% of patients achieve complete remission with available drugs. This reflects the lack of drugs acting on target sites for which there is strong evidence of pathogenicity and the inability to identify responder patients. No criteria for responsiveness are available, exposing patients to unpredictable failures and unpredictable side effects. These individuals are at particular risk for adverse drug reaction (ADRs) or therapeutic failure. Genetic profiling with the Affymetrix drug metabolizing enzymes and transports genotyping array offers the ability to determine 1,931 variants and 225 genes involved in drug metabolism and disposition. Accordingly, the study of well-known drug-metabolizing genes can be involved in the specific metabolic pathway of a drug, which is more likely to define genotype-phenotype association and thereby genotype profiles relevant to drug response that can be applied as predictive biomarkers for pharmacological treatment.

Dataset Information

Autoantibodies in myasthenia gravis: cluster analysis and clinical correlations.

Objective

Methods

Results

Conclusion

Publications

Autoantibodies in myasthenia gravis: cluster analysis and clinical correlations.

Similar Datasets

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