The synaptic dysfunction in myasthenia gravis (MG) is caused by a deficiency of the nicotonic postsynaptic acetylcholine receptor (AChR) protein. The AChR deficiency in acquired MG is caused by an autoimmune attack on the postsynaptic membrane. Immunoglobulin G (IgG) can be localized at the MG end-plate with peroxidase-labelled staphylococcal protein A, and the third component of complement (C3) can be demonstrated with peroxidase-labelled anti-human C3 under experimental conditions, which give excellent ultrastructural localization, optimal preservation of fine structure and minimum background staining. Both IgG and C3 are found on segments of the postsynaptic membrane and on degenerated fragments of the junctional folds in the synaptic space. The abundance of the immune complexes is proportionate to the MEPP amplitude, and hence to the amount of AChR remaining at the end-plate. This indicates that the immune complexes act not merely by impairing AChR function, but primarily by inducing a deficiency of AChR. Parallel electron cytochemical and immunoelectron microscopic studies in chronic experimental autoimmune MG (EAMG) of the rat, demonstrate a deficiency of the postsynaptic AChR and localize IgC and C3 at the end-plate. As in the human disease, the decrease in AChR is more marked and the immune complexes that bind to the postsynaptic membrane are less abundant in the more severely affected animals than in the less severely affected ones. These findings support the assumption that EAMG is a valid model of acquired MG.
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