Heterogeneity of Acetylcholine Receptor Autoantibody-Mediated Complement Activity in Patients With Myasthenia Gravis

The objective of this study was to develop a cell-based assay that measures AChR autoantibody–mediated complement membrane attack complex (MAC) formation. Methods An HEK293T cell line—modified using CRISPR/Cas9 genome editing to disrupt expression of the complement regulator genes (CD46, CD55, and CD59)—was used to measure AChR autoantibody–mediated MAC formation through flow cytometry. Results Serum samples (n = 155) from 96 clinically confirmed AChR MG patients, representing a wide range of disease burden and autoantibody titer, were tested along with 32 healthy donor (HD) samples. AChR autoantibodies were detected in 139 of the 155 (89.7%) MG samples through a cell-based assay. Of the 139 AChR-positive samples, autoantibody-mediated MAC formation was detected in 83 (59.7%), whereas MAC formation was undetectable in the HD group or AChR-positive samples with low autoantibody levels. MAC formation was positively associated with autoantibody binding in most patient samples; ratios (mean fluorescence intensity) of MAC formation to AChR autoantibody binding ranged between 0.27 and 48, with a median of 0.79 and an interquartile range of 0.43 (0.58–1.1). However, the distribution of ratios was asymmetric and included extreme values; 16 samples were beyond the 10–90 percentile, with high MAC to low AChR autoantibody binding ratio or the reverse. Correlation between MAC formation and clinical disease scores suggested a modest positive associati...
Source: Neurology Neuroimmunology and Neuroinflammation - Category: Neurology Authors: Tags: Autoimmune diseases, Myasthenia Research Article Source Type: research