Novel autoantibodies against muscle‐cell membrane proteins in patients with myositis

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Abstract
Objective. To search for autoantibodies against muscle cell-specific surface membrane antigens in patients with inflammatory myopathies. Methods. A cell enzyme-linked immunosorbent assay (cell ELISA) using a human rhabdomyosarcoma cell line (TE-671) was developed and performed in serial dilutions with either nonfixed or fixed cells. A total of 141 different patient sera were tested: 90 from patients with various rheumatic diseases, 12 from patients with cardiomyopathies, 25 from patients with other muscular diseases, and 14 from patients who had undergone major surgery or who had other noninflammatory diseases. As controls, 20 sera were obtained from healthy donors. Results were correlated using immunofluorescence staining and flow cytometry. Results. Using the nonfixed cell ELISA, the proportions of positive sera from the patient groups with rheumatic diseases were 71% with polymyositis (PM), 15% with dermatomyositis (DM), 18% with systemic sclerosis (SSc), 15% with systemic lupus erythematosus (SLE), and 7% with rheumatoid arthritis. Sera from healthy donors, as well as sera from patients with nonrheumatic diseases, did not show significant reactivities. When other cell lines, including a chondrosarcoma, a bladder carcinoma, a pancreas carcinoma, and human foreskin fibroblasts, were used as substrates, positive sera did not react in the cell ELISA. Results obtained with the cell ELISA system using nonfixed cells were confirmed by flow cytometry and immunofluorescence staining. A strong protein band of 50 kd was detected on plasma membrane preparations from TE-671 muscle cells in 33% of PM sera (n = 12). Conclusion. In most sera from patients with PM, DM, and some other rheumatic diseases (i.e., SSc and SLE), autoantibodies directed against muscle-cell surface antigens can be detected. Since these molecules are localized in the muscle-cell surface membrane, autoantibodies directed against these antigens could play a major role in the pathogenesis of PM.