IgG from "seronegative" myasthenia gravis patients binds to a muscle cell line, TE671, but not to human acetylcholine receptor.
Antibodies to acetylcholine receptor (AChR) are found in 85% of patients with myasthenia gravis (seropositive MG [SPMG]) and are thought to be pathogenic; but in 15% of MG patients, the standard immunoprecipitation test for anti-AChR is negative (seronegative MG [SNMG]). Here, we used a novel approach, fluorescence-activated cell sorting analysis, to measure binding of SPMG and SNMG IgG antibodies to rhabdomyosarcoma cell lines that express human adult (TE671-epsilon) or fetal (TE671-gamma) AChR, and to human embryonic kidney (HEK) fibroblasts that express adult human AChR (HEK-AChR). We found that whereas most SPMG antibodies bind to all three cell lines, IgG from 8 of 15 SNMG sera/plasmas bind to the surface of both TE671 cell lines but not to HEK-AChR cells. These results indicate that SNMG antibodies bind to a muscle surface antigen that is not the AChR, which strongly supports previous studies that suggest that SNMG should be considered a distinct subtype of MG.
Blaes
F
F
Department of Clinical Neurology, Institute of Molecular Medicine, University of Oxford, UK.
Beeson
D
D
Plested
P
P
Lang
B
B
Vincent
A
A
D000328:Adult; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood / Q000302:isolation & purification* / Q000494:pharmacology; D005333:Fetus / Q000166:cytology; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000302:isolation & purification* / Q000494:pharmacology; D007668:Kidney / Q000166:cytology; D019042:Muscle Neoplasms; D009157:Myasthenia Gravis / Q000276:immunology*; D011950:Receptors, Cholinergic / Q000276:immunology* / Q000378:metabolism; D018233:Rhabdomyosarcoma, Embryonal; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000276:immunology
D001323:Autoantibodies; D007074:Immunoglobulin G; D011950:Receptors, Cholinergic