MYASTHENIA GRAVIS-LIKE SYNDROME INDUCED BY EXPRESSION OF INTERFERON-GAMMA IN THE NEUROMUSCULAR-JUNCTION

Abnormal humoral responses toward motor end plate constituents in musc le induce myasthenia gravis (MG). To study the etiology of this diseas e, and whether it could be induced by host defense molecules, we exami ned the consequences of interferon (IFN) gamma production within the n euromuscular junction of transgenic mice. The transgenic mice exhibite d gradually increasing muscular weakness, flaccid paralysis, and funct ional disruption of the neuromuscular junction that was reversed after administration of an inhibitor of acetylcholinesterase, features whic h are strikingly similar to human MG. Furthermore, histological examin ation revealed infiltration of mononuclear cells and autoantibody depo sition at motor end plates. Immunoprecipitation analysis indicated tha t a previously unidentified 87-kD target antigen was recognized by ser a from transgenic mice and also by sera from the majority of human MG patients studied. These results suggest that expression of IFN-gamma a t motor end plates provokes an autoimmune humoral response, similar to human MG, thus linking the expression of this factor with development of this disease.