Idiotypic network connectivity and a possible cause of myasthenia gravis.

Extensive idiotypic connectivity has been discovered between the antibodies composing the immune responses against the acetylcholine receptor (AChR) and alpha-1,3-dextran. The idiotypic connections form an elaborate network linking these disparate antigen systems, and there is an hierarchical organization of the antibodies in this network. The key anti-Ids that interconnect these two responses are more crossreactive, lower-affinity antibodies. Interestingly, 15% of patients with MG, which is caused by autoantibodies against the AChR, have serum antibodies against DEX. Control sera are negative for anti-DEX antibodies. Certain anti-DEX antibodies also bind to anti-AChR antibodies via idiotypic interactions. These findings suggest a model for the initiation of autoimmunity in MG. Antibodies made in response to DEX epitopes on the surface of certain bacteria would elicit the production of anti-Ids. However, some of these anti-Ids would also be autoantibodies against the AChR. Thus, is some circumstances, autoimmunity may develop as a consequence of the normal operation of regulatory idiotypic networks.