Passively transferred experimental autoimmune myasthenia gravis. Sequential and quantitative study of the motor end-plate fine structure and ultrastructural localization of immune complexes (IgG and C3), and of the acetylcholine receptor.
Experimental autoimmune myasthenia gravis (EAMG) was passively transferred with immunoglobulin from rats with chronic EAMG to normal recipients. IgG and C3 were localized on terminal expansions of junctional folds of end-plates by 6 hours. Segments of folds rich in acetylcholine receptor (AChR) and coated with IgG and C3 were shed into the synaptic space by 24 hours, resulting in AChR deficiency of the postsynaptic membrane. Many sensitized postsynaptic regions were destroyed by macrophages by day 2, but effective nerve-muscle contacts were reestablished by day 5. On day 10, end-plates were still structurally abnormal and showed AChR deficiency, but the animals were clinically recovered. On day 54, postsynaptic regions were still reduced in size, with slight reduction of postsynaptic AChR. Throughout the study, the miniature end-plate potential amplitude tended to vary directly with morphometric estimates of the abundance of the postsynaptic membrane reacting for AChR. Complement-mediated injury to the junctional folds and opsonization of the postsynaptic region can explain the morphologic changes. It is not yet known why phagocytic invasion of the end-plate occurs in acute EAMG and in passively transferred EAMG induced by chronic EAMG immuglobulin, but not in chronic EAMG and only rarely in the human disease.
D000818:Animals; D000936:Antigen-Antibody Complex; D001327:Autoimmune Diseases / Q000276:immunology*; D003176:Complement C3 / Q000032:analysis / Q000276:immunology; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000032:analysis; D009045:Motor Endplate / Q000276:immunology / Q000648:ultrastructure*; D009157:Myasthenia Gravis / Q000276:immunology*; D009469:Neuromuscular Junction / Q000648:ultrastructure*; D051381:Rats; D011950:Receptors, Cholinergic / Q000276:immunology*
D000936:Antigen-Antibody Complex; D003176:Complement C3; D007074:Immunoglobulin G; D011950:Receptors, Cholinergic