Antigen mimicry in autoimmune disease. Can immune responses to microbial antigens that mimic acetylcholine receptor act as initial triggers of Myasthenia gravis?

Myasthenia gravis (MG) is an autoimmune disease caused by autoantibodies against self acetylcholine receptor (AChR). Although a great deal of information is known about the molecular and cellular parameters of the disease, its initial trigger is not known. In order to study the possibility of the involvement of microbial antigens that mimic AChR in triggering MG, we have searched the microbial proteins in the data bank for regions that are similar in structure to the regions of human (h) AChR alpha chain recognized by autoAbs in MG patients. Hundreds of candidate structures on a large number of bacterial and viral proteins were identified. To test the feasibility of the idea, we synthesized four microbial regions similar to each of the major autodeterminants of hAChR (alpha12-27, alpha111-126, alpha122-138, alpha182-200) and investigated their ability to bind autoAbs in MG and normal sera controls. It was found that MG sera recognized a significant number of these microbial regions. The results indicate that in some MG cases immune responses to microbial antigens may cross-react with self antigen (in this case hAChR) and could constitute initial triggers of the disease.