Specificities of antibodies to acetylcholine receptors in sera from myasthenia gravis patients measured by monoclonal antibodies.

Abstract

The pattern of antibody specificities in sera from patients with myasthenia gravis (MG) was determined by the ability of monoclonal antibodies against defined determinants on the acetylcholine receptor molecule to inhibit binding of the serum antibodies to receptor from human muscle. MG patients produce fundamentally the same pattern of specificities as that produced by animals immunized with receptor purified from fish electric organs or mammalian muscle. Most of the antibodies are directed at the main immunogenic region which is located on the extracellular surface of the .alpha. subunit and is distinct from the acetylcholine binding site. Regions on the .beta. and .gamma. subunits near the main immunogenic region are also significantly immunogenic. In 1 patient the proportions of antibodies to various regions are constant over time despite changes in total antibody amount and clinical state. Between patients there is no obvious correlation between antibody specificities and clinical state. The autoimmune response in MG is probably stimulated by human receptor rather than a crossreacting (e.g., viral) antigen. In both MG and experimental autoimmune MG the pattern of specificities produced is probably determined by the inherently immunogenic structural features of the receptor molecule. The wide differences in clinical state sometimes observed between patients with the same total concentration of antireceptor antibody may be due primarily to differences in endogenous factors which affect the safety factor for neuromuscular transmission rather than to the presence of especially pathogenic antireceptor specificities.