Detection of autoantibodies associated with the disease myasthenia gravis

摘要

This invention is directed towards peptidic compositions, methods, and diagnostic kits for the accurate and sensitive detection of human acetylcholine receptor (AChR) autoantibodies associated with the disease myasthenia gravis (MG). Eighteen synthetic overlapping oligopeptides encompassing the entire extracellular domain (residues &agr; 1-210) of the &agr;-chain of human AChR and an additional peptide (residues . alpha.262-276) corresponding to the extracellular connection between the two transmembrane regions were prepared. The immunologic reactivity of these peptides against autoantibodies in the plasma of patients with MG was ascertained by solid-phase radioimmunoassay. Autoantibody responses were subjected to genetic regulation as indicated by the variation in recognition profiles from patient to patient. However, it was possible to detect AChR autoantibodies in a heterogenous patient population by employing a peptide mixture comprising at least four peptides (SEQ ID NOS. 8, 17, 18, and 23). These peptides correspond to the following regions of the AChR: &agr;12-27, &agr;111-126, &agr;122-138, and &agr;182- 198. These reagents provide a peptide-based direct antibody binding method for the detection of myasthenogenic autoantibodies.