title: Pathogenesis of hyperacute experimental autoimmune myasthenia gravis. Acetylcholine receptor/cholinergic site/receptor function/autoimmunity.
abstract: Three mAbs, mAbs 249E, 370, and 383C, directed against the alpha-bungarotoxin (alpha BgTx) binding site of the acetylcholine receptor (AChR) induce a hyperacute form of experimental autoimmune myasthenia gravis (EAMG), characterized by death within hours of mAb injection. To analyze the mechanisms of this effect, purified AChR-mAb complexes were investigated for their ability to bind the cholinergic agonist carbamoylcholine and to undergo agonist-induced activation of the cholinergic ionophore. The three mAbs inhibited carbamylcholine binding, and, conversely, their binding to AChR was inhibited by carbamylcholine. All three completely inhibited carbamylcholine-induced T1+ influxes to AChR-rich vesicles. These data indicate that the severe hyperacute EAMG induced by these mAbs results from blockage of AChR function and that the role of such potent Abs (even if present in small amounts) in the pathogenesis of human myasthenia gravis deserves further investigation.
authors.affiliation: Department of Medicine, Duke University, Durham, NC 27710.
authors.forename: M
authors.initials: M
authors.lastname: Mihovilovic
authors.forename: D
authors.initials: D
authors.lastname: Donnelly-Roberts
authors.forename: D P
authors.initials: DP
authors.lastname: Richman
authors.forename: M
authors.initials: M
authors.lastname: Martinez-Carrion
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology; D015551:Autoimmunity; D002038:Bungarotoxins / Q000378:metabolism / Q000494:pharmacology; D002217:Carbachol / Q000378:metabolism / Q000494:pharmacology; D018680:Cholinergic Antagonists; D004195:Disease Models, Animal; D006801:Humans; D066298:In Vitro Techniques; D009157:Myasthenia Gravis / Q000209:etiology* / Q000276:immunology / Q000378:metabolism; D051381:Rats; D011950:Receptors, Cholinergic / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D002038:Bungarotoxins; D018680:Cholinergic Antagonists; D011950:Receptors, Cholinergic; D002217:Carbachol