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.



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).



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).



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.
Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Saif
S
Huda
Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Mark R
MR
Woodhall
Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Angela
A
Vincent
Division of Neurology, E8-74, Department of Medicine, University of Cape Town, South Africa.
Jeannine M
JM
Heckmann
D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000453:epidemiology / Q000276:immunology*; D016017:Odds Ratio; D020794:Receptor Protein-Tyrosine Kinases / Q000276:immunology*; D011950:Receptors, Cholinergic / Q000276:immunology*; D013019:South Africa / Q000453:epidemiology
D001323:Autoantibodies; D026502:LDL-Receptor Related Proteins; C551781:LRP4 protein, human; D011950:Receptors, Cholinergic; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; C095714:MUSK protein, human; D020794:Receptor Protein-Tyrosine Kinases
AChR; Africa; LRP4; MuSK; cell-based assay; myasthenia gravis