ABSTRACT
The distribution of autoantibodies was studied in patients with rheumatoid arthritis (RA) treated by D-penicillamine and who developed myasthenia gravis (MG). The anti-human acetylcholine receptor (AChR) antibodies were specifically associated with clinical symptoms of MG without any difference in the pattern of specificities in idiopathic (id-MG) or in induced MG (DPen-MG). Conversely, anti-nuclear antibodies were elevated in DPen-MG sera compared to id-MG sera (P less than 0.001) but were also compared to patients with RA treated by D-penicillamine (or thiopronine) and who did not develop MG. Anti-denatured DNA antibodies were enhanced in sera from treated patients, whether they had presented or not a MG disease. Anti-histone antibodies were associated with RA. These observations suggest that the immunological imbalance in RA patients, can be increased by a drug treatment which may trigger the appearance of a second autoimmune disease such as MG, where anti-AChR antibodies are associated with anti-nuclear antibodies.
Subject(s)
Arthritis, Rheumatoid/immunology , Autoantibodies/analysis , Myasthenia Gravis/immunology , Penicillamine/adverse effects , Adult , Aged , Antibodies, Antinuclear/analysis , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/drug therapy , Enzyme-Linked Immunosorbent Assay , Female , Fluorescent Antibody Technique , Humans , Male , Middle Aged , Myasthenia Gravis/etiology , Penicillamine/immunology , Receptors, Cholinergic/immunologyABSTRACT
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.
Subject(s)
Epitopes/immunology , Myasthenia Gravis/chemically induced , Penicillamine/adverse effects , Adult , Aged , Aged, 80 and over , Antibody Formation , Arthritis, Rheumatoid/drug therapy , Binding, Competitive , Female , Humans , Male , Middle Aged , Myasthenia Gravis/immunology , Receptors, Cholinergic/immunologyABSTRACT
Sera from 23 patients with D-penicillamine-induced myasthenia gravis (MG) contained antibodies directed against the human muscle acetylcholine receptor (anti-AChR) in 83% of the cases at the onset of the disease. Twenty-one were patients with rheumatoid arthritis. The anti-AChR antibody titers were comparable to those of sera from ocular MG patients and were related to the presence of clinical signs but not to their severity. The anti-AChR antibodies persisted in autonomous MG (5 cases) and disappeared in the other cases. The same phenomenon occurred for antinuclear antibodies detected in sera from 13 patients at the onset of the disease: anti-ss DNA 9/13, antinuclear 4/13 and anti-histones 7/13. The latter antibodies seem to result from, and follow the D-penicillamine treatment.