Immune complexes (IgG and C3) at the motor end-plate in myasthenia gravis: ultrastructural and light microscopic localization and electrophysiologic correlations.
Although there is strong evidence that myasthenia gravis (MG) is caused by an autoimmune reaction to the nicotinic postsynaptic acetylcholine receptor (AChR) protein, immune complexes have never been directly demonstrated at the end-plate by immunocyto-chemistry or immunoelectron microscopy. Staphylococcal protein A (which binds to the Fc region of human IgG subclasses 1, 2, and 4) and rabbit anti-human C3 conjugated with peroxidase were used for the ultrastructural (5 patients) and light microscopic (12 patients) localization of IgG and C3, respectively, at MG end-plates. Both IgG and C3 were localized on segments of the postsynaptic membrance and fragments of degenerating junctional folds in the synaptic space. In nonmyasthenic control patients no immune complexes were evident at the end-plate. As judged by morphometric analysis of electron micrographs, the immune complexes were more abundant in the less severely affected MG patients than in the more severely affected ones. A linear correlation was demonstrated between the length of the postsynaptic membrance binding immune complexes and the amplitude of the miniature end-plate potential. The less intense reaction for immune complexes in the more severely affected MG patients can be attributed to the smaller quantity of AChR remaining at their end-plates. The findings provide unambiguous evidence for a destructive auto-immune reaction involving the postsynaptic membrance in MG. Immunopharmacologic blockade of AChR and IgG-induced modulation of AChR may also contribute to the AChR deficiency at the MG end-plates.
D000328:Adult; D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D001426:Bacterial Proteins; D003176:Complement C3; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D008297:Male; D008564:Membrane Potentials; D008854:Microscopy, Electron; D008875:Middle Aged; D009045:Motor Endplate / Q000276:immunology* / Q000502:physiology; D009157:Myasthenia Gravis / Q000276:immunology*; D009469:Neuromuscular Junction / Q000276:immunology*; D010544:Peroxidases; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D013210:Staphylococcus; D014965:X-Rays
D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D001426:Bacterial Proteins; D003176:Complement C3; D007074:Immunoglobulin G; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D010544:Peroxidases