CHARACTERISTICS OF ACETYLCHOLINE-RECEPTOR-ANTIBODY-NEGATIVE MYASTHENIA GRAVIS IN A SOUTH AFRICAN COHORT

Introduction: 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 (n530; 2006-2012) and AChR, MuSK, and LRP4 RIA with or without cell-based assays (CBA) (n553; 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.