Role of complement in the pathogenesis of experimental autoimmune myasthenia gravis.

TLDR

Experimental autoimmune myasthenia gravis in Lewis rats shows an acute phase early after immunization with AChR and Bordetella pertussis adjuvant, characterized by a destructive cellular attack on postsynaptic muscle membranes that can be passively transferred by IgG from chronically affected rats. The study aimed to determine whether complement depletion with cobra venom factor could inhibit acute EAMG induced by passive antibody transfer or active immunization. Complement depletion was achieved by cobra venom factor treatment, which was applied to rats receiving either passive syngeneic anti‑AChR antibodies or active immunization to induce acute EAMG. Complement depletion prevented the pathogenic effects of anti‑AChR antibodies: passive transfer of excess antibodies had no measurable effect on muscle AChR content or neuromuscular transmission, indicating complement is a critical mediator of antibody‑induced neuromuscular dysfunction in vivo.

Abstract

An acute phase of experimental autoimmune myasthenia gravis (EAMG) occurs transiently early in the immune response of Lewis rats to nicotinic acetylcholine receptors (AChR) when Bordetella pertussis is used as adjuvant. It is characterized by a destructive cellular attack directed at the postsynaptic membranes of muscle. Acute EAMG can be passively transferred to normal rats by IgG from serum of rats with chronic EAMG. In the present study, acute EAMG, induced either by passive transfer of syngeneic antibodies or by active immmunization, was inhibited in rats depleted of complement by treatment with cobra venom factor (CoF). Furthermore, passive transfer of antibodies in excess of the muscle's content of AChR was without any measurable effect in rats treated with CoF. Although 60% of the muscle's AChR was complexed with antibody, there was no reduction in the muscle's content of AChR, and neuromuscular transmission was not compromised as judged electromyographically by curare sensitivity. These data imply that redistribution, accelerated degradation, and impairment of the ionophore function of AChR, effects of antibodies described in vitro on extrajunctional AChR, do not play a significant role in vivo in impairing neuromuscular transmission in an intact neuromuscular junction. Complement appears to be a critical mediator of anti-AChR antibodies' pathogenicity in vivo.