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

Myasthenia gravis (MC) is an Ab-mediated autoimmune neuromuscular dise ase and is linked to MHC class II beta-chain polymorphism. Corticoster oids and azathioprine are the primary immunosuppressive drugs used in the treatment of MG. These drugs have significant side effects and hav e limited efficacy. Therefore, drugs with fewer side effects and great er efficacy are being sought. IFN-alpha is a potent immunomodulator an d has been shown to down-regulate MHC class II expression on lymphoid cells. MHC class II expression is critical for the development of expe rimental autoimmune myasthenia gravis (EAMG). Because of the immunomod ulating effects of IFN-alpha and its effect on the MHC class II expres sion, 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 we ll established, reduced the incidence of clinical EAMG by more than 50 % in two separate experiments (p = 0.04 and 0.008). Therefore, IFN-alp ha could be a potential agent for the control of MG, and other Ab-medi ated autoimmune diseases.