Pathological Mechanisms in Experimental Autoimmune Myasthenia Gravis

Immunization of mammals with purified acetylcholine receptor protein (AChR) 1 results in an autoimmune response to skeletal muscle AChR which impairs neuromuscular transmission, causing experimental autoimmune myasthenia gravis (EAMG). In the introduction to the accompanying article (1) the striking similarities between EAMG and the human disease myasthenia gravis (MG) were reviewed. In that article we showed that immunization of rats with purified syngeneic AChR protein or AChR from fish electric organs induced an autoimmune response to muscle AChR. Antibodies to AChR were found both free in serum and bound to muscle AChR. Also, a large decrease in AChR content was noted. In this paper we investigate the role of antibodies to AChR in the impairment of neuromuscular transmission in EAMG by passively transferring antibody from rats with EAMG to normal rats. Passive transfer experiments are intended to clarify the relative contribution of cell-mediated and humoral immunity to causing the changes in AChR function, AChR content, and postsynaptic membrane structure which are responsible for impairment of neuromuscular transmission. Previous experiments suggest that passive transfer of EAMG with antibody should be possible. Antisera from animals with EAMG block AChR activity on muscle (2, 3) and electric organ cells (4-6) in vitro. Chronic administration to mice of large amounts of immunoglobulin from patients with MG resulted in decreased miniature endplate potential amplitude and diminished toxin binding to end-plates (7). High titers of antibody to AChR have been found in the serum of babies suffering from