Myasthenia gravis without acetylcholine-receptor antibody: a distinct disease entity.
Immunoglobulin preparations from eight patients with clinical features of myasthenia gravis, in whom no serum antibody against acetylcholine receptor (AChR) could be detected, were injected intraperitoneally into mice. Neuromuscular transmission was significantly impaired compared with mice receiving control human immunoglobulin. No antibody bound to the mouse AChR was detected, but there was a small loss (9.4%) of AChR in the mouse diaphragms. Mice injected with myasthenic AChR-antibody-positive immunoglobulin and mice growing hybridoma cells secreting monoclonal AChR antibody showed similar impairment of neuromuscular transmission, but 75% and 94%, respectively, of their muscle AChR had antibody bound and AChR losses were 47% and 60%. The results suggest that a pathogenetic immunoglobulin antibody interferes with neuromuscular transmission in these AChR-antibody-negative patients by binding to non-AChR determinants at the neuromuscular junction. This form of myasthenia is immunologically and physiologically distinct from the AChR-antibody-positive form.
S
S
Mossman
A
A
Vincent
J
J
Newsom-Davis
D000293:Adolescent; D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001323:Autoantibodies / Q000032:analysis*; D003964:Diaphragm / Q000276:immunology; D000939:Epitopes; D005260:Female; D006801:Humans; D006825:Hybridomas; D007074:Immunoglobulin G / Q000032:analysis; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008875:Middle Aged; D009045:Motor Endplate / Q000276:immunology*; D009157:Myasthenia Gravis / Q000276:immunology*; D009469:Neuromuscular Junction / Q000276:immunology*; D011863:Radioimmunoassay; D011950:Receptors, Cholinergic / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D000939:Epitopes; D007074:Immunoglobulin G; D011950:Receptors, Cholinergic