IFN-ALPHA TREATMENT SUPPRESSES THE DEVELOPMENT OF EXPERIMENTAL AUTOIMMUNE MYASTHENIA-GRAVIS

Myasthenia gravis (MC) is an Ab-mediated autoimmune neuromuscular disease and is linked to MHC class II beta-chain polymorphism. Corticosteroids and azathioprine are the primary immunosuppressive drugs used in the treatment of MG. These drugs have significant side effects and have limited efficacy. Therefore, drugs with fewer side effects and greater efficacy are being sought. IFN-alpha is a potent immunomodulator and has been shown to down-regulate MHC class II expression on lymphoid cells. MHC class II expression is critical for the development of experimental autoimmune myasthenia gravis (EAMG). Because of the immunomodulating effects of IFN-alpha and its effect on the MHC class II expression, we tested the therapeutic efficacy of IFN-alpha on EAMG induced by immunization with acetylcholine receptor (AChR) in CFA. IFN-alpha (10(5) IU three times weekly for 5 wk) treatment started 1 wk after the second immunization with AChR in CFA, when autoimmunity to AChR is well established, reduced the incidence of clinical EAMG by more than 50% in two separate experiments (p = 0.04 and 0.008). Therefore, IFN-alpha could be a potential agent for the control of MG, and other Ab-mediated autoimmune diseases.