Fine antigenic specificities of antibodies in sera from patients with D-penicillamine-induced myasthenia gravis

Abstract

A small fraction of patients with rheumatoid arthritis and other diseases on D-penicillamine treatment may develop antibodies against the acetylcholine receptor (AChR) and symptoms of myasthenia gravis (MG). The mechanism leading to this phenomenon is not known. We have studied the fine antigenic specificities of the anti-AChR antibodies in 19 D-penicillamine-induced MG (pen-MG) patients and compared them with those of antibodies from 204 idiopathic MG patients (the data for 122 obtained from earlier experiments). Antigenic specificities of the circulating antibodies were determined by the capacity of monoclonal antibodies (MoAbs), against certain determinants on the AChR, to inhibit binding of the serum antibodies to the AChR. Monoclonal antibodies against alpha, beta and gamma subunits were used. The anti-AChR antibody patterns of pen-MG patients were very similar to those of idiopathic MG patients. Antibodies to the main immunogenic region, which is located on the extracellular surface of the alpha-subunit, were the predominant group. The variations of antibody specificities in serial sera collected from individual patients at different times were usually small, as were those of idiopathic MG. These results strongly suggest that the antibody repertoire in the sera of idiopathic and pen-MG patients is very similar.