Experimental autoimmune myasthenia gravis induced by thymic acetylcholine receptor-like protein.

The trigger mechanism of autoimmunity in myasthenia gravis (MG) has yet to be elucidated. To determine the function of the thymus in the pathogenesis of MG, we tried to produce chronic experimental autoimmune myasthenia gravis (EAMG) using nicotinic acetylcholine receptor-like protein (n-AChR-LP) isolated from the fetal calf thymus (FCT) by affinity chromatography with Sepharose-4B bound cobrotoxin. Lewis rats were inoculated with n-AChR-LP emulsified in Freund's complete adjuvant and later received two booster immunizations. The immunized rats developed generalized hypotonia at seven to ten days and then recovered spontaneously within two weeks. In the fourth week, flaccid paresis with either a hunched posture or waddling gait appeared in half of the rats, these symptoms improved transiently after treatment with neostigmine. At this time, evoked EMG showed decremental responses after curare sensitization, while anti-n-AChR-LP antibody, measured by enzyme-linked immunosorbent assay (ELISA), increased significantly. These findings therefore suggest that the n-AChR-LP from the thymus includes antigens to induce EAMG.