Characteristics of AChR antibody-negative myasthenia gravis in a South African cohort.

We determined the frequencies of antibodies (Abs) directed against muscle specific kinase (MuSK) and lipoprotein receptor-related protein 4 (LRP4) in the sera of a South African cohort of acetylcholine receptor (AChR) antibody-negative generalized MG and determined outcomes to therapies.Sera negative by commercial AChR radioimmunoassay (RIA) were tested by MuSK RIA (n=30; 2006-2012) and AChR, MuSK, and LRP4 RIA ± cell-based assays (CBA) (n=53; 2012-2015).AChR-Abs were detected in 4 of 53 and MuSK-Abs in 20 of 83 (24%). Thirty-six of 53 (68%) negative for MuSK, AChR, and LRP4-Abs were triple-seronegative (triple-SNMG). Individuals with MuSK-MG compared to triple-SNMG had younger onset (P=0.008), more likely African genetic ancestry (P=0.008), 4 times higher odds of reaching MGFA grade IVB/V (P=0.018), but also 9 times more likely to reach at least minimal manifestations status after ≥12 months on therapy (P=0.003).Individuals with African genetic ancestry and severe bulbar/respiratory AChR antibody-negative MG are likely to have MuSK-MG, but most respond favorably to maintenance immunotherapies. This article is protected by copyright. All rights reserved.