AChR-blocking antibodies and complement system dynamics: evaluating their interplay and clinical implications in myasthenia gravis

Abstract

Background: Myasthenia gravis (MG) is an autoimmune disorder characterised by autoantibodies (abs) targeting proteinsat the neuromuscular junction, primarily the acetylcholine receptor (AChR). While the role of AChR-binding abs is well-established, the pathogenicity and clinical relevance of AChR-blocking antibodies in MG, and their association with com-plement system, remain less understood. Aims: This study aims to provide comprehensive insights into the prevalence and interplay of AChR-blocking antibodies andthe complement system in an Argentinian MG cohort, investigating their relationships with disease activity.Methods: We studied 75 MG patients with detectable AChR-binding abs, assessing the presence of AChR-blocking abs andcomplement components C3, C4, and C5a. We also examined clinical severity using the Activities of Daily Living and MGComposite scores. Correlation analyses were made to elucidate associations.Results: AChR-blocking abs were detected in 49.3% of the patients. An inverse correlation was found between AChR-blockingabs titres and disease severity, with a higher titre associated with milder symptoms. Complement analysis revealed higherC4 levels in the AChR-blocking abs positive group, indicating reduced complement activation. Conclusion: Our study provides valuable insights into the prevalence of AChR-blocking antibodies. Higher AChR-blockingabs titres were associated with less severe MG and reduced complement system activation, indicating a potential protectivemechanism for those abs. These fndings suggest that AChR-blocking abs could serve as a potential biomarker for a milderdisease course and highlight the need for further research to understand their role in MG pathology, which will improvestrategies for clinical management and diagnosis.