EXPERIMENTAL AUTOIMMUNE MYASTHENIA GRAVIS AND MYASTHENIA GRAVIS: BIOCHEMICAL AND IMMUNOCHEMICAL ASPECTS*

TLDR

Acetylcholine receptor (AChR) is present in human, rat muscle, and rat thymus, and the chronic phase of experimental autoimmune myasthenia gravis (EAMG) serves as a useful model for human MG due to comparable 7‑S immunoglobulin levels against non‑toxin binding determinants. The study examines how thymoma and disease severity correlate with antibody titers and proposes an AChR‑based assay from human muscle as a diagnostic test for MG. The authors purified and characterized the structure of AChR from *Electrophorus electricus* (eel) using affinity chromatography. Immunization of rats with eel AChR elicits antibodies that partially cross‑react with rat muscle AChR, induces myasthenic symptoms absent with denatured AChR, and the resulting immunoglobulin blocks AChR activity; human MG sera contain 300‑fold higher anti‑AChR antibodies than controls, and assays using rat or eel AChR yield markedly lower titers than human AChR.

Abstract

Stucture of acetylcholine receptor protein (AChR) purified from Electrophorus electricus (eel) by affinity chromatography is described. AChR is detected in extracts from human muscle, rat muscle, and rat thymus. Rats immunized with eel AChR develop humoral antibodies, a small fraction of which recognize AChR from rat muscle. Rats immunized with AChR exhibit myasthenia, but those immunized with denatured AChR do not. Immunoglobulin fraction of antisera to eel AChR can block the activity of AChR in electroplaques. Sera from patients with myasthenia gravis contain antibodies to AChR from human muscle detectabe at an average value 300-fold the background level in sera from nonmyasthenics. Relationship of thymoma and disease intensity to antibody titer is examined. The chronic phase of EAMG appears a good model of MG, since in both cases similar concentrations of 7-S immunoglobulin against determinants on muscle AChR other than the toxin binding site are found. Assay of anti-AChR antibody in sera from MG patients using AChR from rat muscle gives titers 10%-15% of those obtained using AChR from human muscle, and using AChR from eel gives negligible titers. The assay method described for assaying antibodies against AChR from human muscle is suggested as a diagnostic test for MG.