Molecular Mimicry and Microorganisms: A Role in the Pathogenesis of Myasthenia Gravis?

Abstract

Myasthenia gravis (MG) is a human disease characterized by excessive fatigability and weakness. The disease was originally described by Thomas Willis in 1672 (Herrmann 1967). However, the pathogenesis remained largely a mystery until Patrick and Lindstrom (1973) made a spectacular discovery. They were attempting to raise antibodies against the nicotinic acetylcholine receptor (AchR) by immunizing rabbits with AchR isolated from fish electric organs. Interestingly, the rabbits became sick with a disease that both clinically and electrophysiologically was similar to MG and could be reversed with acetylcholine esterase inhibitors (Grob et al. 1981; Lindstrom 1979). They had developed an animal model for MG. Subsequent work demonstrated that the animal disease could be passively transferred to other animals by antibodies from the actively immunized animals (Lindstrom et al. 1976a), and animals could be made myasthenic by antibodies from the sera of patients with MG. More recently, it has been shown that the experimental disease can be induced with monoclonal antibodies against the α-chain of AchR (Gomes et al. 1981). It was concluded that MG is caused by a humoral immune response against the AchR.