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 ag ainst self acetylcholine receptor (AChR). Although a great deal of informat ion is known about the molecular and cellular parameters of the disease, it s initial trigger is not known. In order to study the possibility of the in volvement of microbial antigens that mimic AChR in triggering MG, we have s earched the microbial proteins in the data bank for regions that are simila r in structure to the regions of human (h) AChR or chain recognized by auto Abs in MG patients. Hundreds of candidate structures on a large number of b acterial and viral proteins were identified. To test the feasibility of the idea, we synthesized four microbial regions similar to each of the major a utodeterminants of hAChR (alpha 12-27, alpha 111-126, alpha 122-138, alpha 182-200) and investigated their ability to bind autoAbs in MG and normal se ra controls. It was found that MG sera recognized a significant number of t hese microbial regions. The results indicate that in some MG cases immune r esponses to microbial antigens may cross-react: with self antigen tin this case hAChR) and could constitute initial triggers of the disease. (C) Ameri can Society for Histocompatibility and Immunogenetics, 2000. Published by E lsevier Science Inc.