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 proteins at 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 complement system, remain less understood.

Aims: This study aims to provide comprehensive insights into the prevalence and interplay of AChR-blocking antibodies and the 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 and complement components C3, C4, and C5a. We also examined clinical severity using the Activities of Daily Living and MG Composite 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-blocking abs titres and disease severity, with a higher titre associated with milder symptoms. Complement analysis revealed higher C4 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-blocking abs titres were associated with less severe MG and reduced complement system activation, indicating a potential protective mechanism for those abs. These findings suggest that AChR-blocking abs could serve as a potential biomarker for a milder disease course and highlight the need for further research to understand their role in MG pathology, which will improve strategies for clinical management and diagnosis.