Characteristics Of acetylcholine‐receptor‐antibody–negative myasthenia gravis in a South African cohort

In this study 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 with acetylcholine receptor (AChR)‐antibody–negative generalized MG and determined outcomes to therapies. Methods Sera negative by commercial AChR radioimmunoassay (RIA) were tested by MuSK RIA ( n  = 30; 2006–2012) and AChR, MuSK, and LRP4 RIA with or without cell‐based assays (CBA) ( n  = 53; 2012–2015). Results AChR‐Abs were detected in 4 of 53 and MuSK‐Abs in 20 of 83 (24%) cases. Thirty‐six of 53 (68%) were triple seronegative (triple‐SNMG) for MuSK, AChR, and LRP4‐Abs. When compared with triple‐SNMG, individuals with MuSK‐MG had a younger onset age ( P  = 0.008), a greater likelihood of African genetic ancestry ( P  = 0.008), and 4‐fold higher odds of reaching MGFA grade IVB/V ( P  = 0.018), but were also 9‐fold more likely to reach at least minimal manifestations status after ≥12 months of therapy ( P  = 0.003). Conclusions Individuals with African genetic ancestry and severe bulbar/respiratory AChR‐Ab–negative MG are likely to have MuSK‐MG, but most respond favorably to maintenance immunotherapies. Muscle Nerve 54 : 1023–1029, 2016