The immunopathology of acquired myasthenia gravis.
Specific probes (alpha-bungarotoxin for acetylcholine receptor (AChR), staphylococcal protein A for IgG, monospecific antibodies against C3 and C9) labelled with peroxidase were applied to study of the ultrastructure of the MG end plate. In each case of MG there was postsynaptic AChR deficiency, usually greatest at end plates with marked degeneration of junctional folds. Morphometric estimates of postsynaptic AChR correlated linearly with the MEPP amplitude. In each case of MG, IgG was localized on the postsynaptic membrane where AChR is known to be located and on debris in the synaptic space. The abundance of antibody was proportionate to the amount of AChR remaining at the end plate. The localization of C3 was essentially identical with that of IgG. For most cases of MG it can be inferred that binding of IgG and C3 to AChR does not interfere with receptor function. C9, the terminal lytic complement component, was localized on debris in the synaptic space and on remnants of junctional folds. This proves that complement mediated destruction of junctional folds occurs in human MG. Studies in experimental auto-immune MG indicate that antibody-dependent internalization of AChR occurs in subclinical, mild and more severe diseases but increased AChR synthesis can compensate for this in subclinical and mild myasthenia. Complement-mediated injury of the postsynaptic membrane appears to be a requirement for induction of more severe MG.
D003167:Complement Activation; D003165:Complement System Proteins / Q000032:analysis; D006651:Histocytochemistry; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D009045:Motor Endplate / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D009157:Myasthenia Gravis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009469:Neuromuscular Junction / Q000276:immunology*; D011950:Receptors, Cholinergic / Q000032:analysis*
D007074:Immunoglobulin G; D011950:Receptors, Cholinergic; D003165:Complement System Proteins