Ultrastructural localization of immune complexes (IgG and C3) at the end-plate in experimental autoimmune myasthenia...

Rats immunized with purified torpedo acetylcholine receptor (AChR) plus adjuvants developed chronic experimental autoimmune myasthenia gravis (EAMG) after day 28. Forelimb muscles from EAMG rats 29 to 103 days after immunization and from control animals were used for the ultrastructural localization of IgG and C3. IgG was demonstrated with rabbit anti-rat IgG followed by treatment with peroxidase-labeled staphylococcal protein A; and C3 with peroxidase-labeled rabbit anti-rat C3, or with unlabeled rabbit anti-rat C3 followed by peroxidase-labeled protein A. In EAMG rats both IgG and C3 were localized on the terminal expansions of the junctional folds, where AChR is known to be located, and on detached, degenerated parts of the folds in the synaptic space. Background staining was negligible. The findings provide unambiguous evidence for a destructive autoimmune reaction involving the postsynaptic membrane in EAMG, implicate the complement system in this reaction and show that detachment of the tips of the junctional folds is one way by which immune complexes, and AChR, are eliminated from the postsynaptic membrane. The immuno-electron microscopic findings in chronic EAMG closely resemble those described in human myasthenia gravis.