Myasthenia induced by monoclonal anti-acetylcholine receptor antibodies: clinical and electrophysiological aspects

Abstract

To investigate individual components of the humoral immune response directed against the acetylcholine receptor in experimental myasthenia, we injected monoclonal antireceptor antibody into normal rats. These antibodies were produced by cloned hybridoma lines formed by fusion of immune spleen cells with the myeloma cell line P3-X63-Ag8. Antibodies from two of seven clones induced acute experimental myasthenia, manifested by clinical weakness, decremental electromyographic response to repetitive nerve stimulation, and diminished mean amplitudes of miniature end-plate potentials (mepps): 0.55 +/- 0.02 mv (SEM) versus 0.71 mv for controls (p less than 0.001). In clinically affected animals, mepp amplitudes from the diaphragm correlated with decremental responses in the gastronemius muscle (r = -0.91, p less than 0.01). The results suggest that binding of a single antibody species to a single determinant on the acetylcholine receptor molecule is sufficient to induce acute experimental myasthenia gravis.