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Myasthenia gravis (MG) is an organ-specific autoimmune disease in which autoantibodies against nicotinic acetylcholine receptors (AChR) at the postsynaptic membrane cause loss of functional AChR and disturbed neuromuscular transmission. The immunopathogenic mechanisms responsible for loss of functional AChR include antigenic modulation by anti-AChR antibodies, complement-mediated focal lysis of the postsynaptic membrane, and direct interference with binding of acetylcholine to the AChR or with ion channel function. The loss of AChR and subsequent defective neuromuscular transmission is accompanied by increased expression of the different AChR subunit genes, suggesting a role for the target organ itself in determining susceptibility and severity of disease. Experimental autoimmune myasthenia gravis (EAMG) is an animal model for the disease MG, and is very suitable to study the immunopathogenic mechanisms leading to AChR loss and the response of the AChR to this attack. In this article the current concepts of the structure and function of the AChR and the immunopathological mechanisms in MG and EAMG are reviewed.

The in vivo effects of neonatal administration of varying doses of anti-idiotype antibodies on serum anti-acetylcholine receptor (AChR) antibody titers, idiotype expression, and disease severity was studied in experimental autoimmune myasthenia gravis. Polyclonal affinity purified anti-idiotype antibodies and monoclonal anti-idiotype antibodies directed at anti-AChR monoclonal antibody 65 were administered in dosages varying from the nanogram to the microgram range. Mab 65 is directed against the main immunogenic region of mammalian AChR. In 1 out of 4 experiments administration of a nanogram dosage of anti-idiotype antibodies led to an enhanced anti-AChR antibody response after immunization with AChR. But no enhancing effect on idiotype expression could be demonstrated during this experiment. Adoptive transfer of spleen cells from rats pretreated with a nanogram dosage of anti-idiotype antibodies resulted in an significantly increased antibody response against rat AChR after immunization. From these experiments we conclude that in vivo administration of polyclonal or monoclonal anti-idiotypes does not reproduceably modify the serum antibody level against the acetylcholine receptor, nor influences the idiotype profile of the immune response. Secondly, the idiotype mediated manipulation of the immune response against large antigens, like the acetylcholine receptor, is clearly more complicated than that against small haptens. Adoptive transfer models, might be helpful in analysing the possibilities of anti-idiotype treatment in myasthenia gravis in more detail.