Antibodies to distinct polypeptides of RNA polymerase I in sera from patients with rheumatic autoimmune disease

Sera from patients with rheumatic autoimmune diseases were screened for antibodies directed against RNA polymerase I by using a solid-phase radioimmunoassay. Significant levels of the antibodies were detected in the sera of all patients with either systemic lupus erythematosus or mixed connective tissue disease and in 78% of the individuals with rheumatoid arthritis. No detectable anti-RNA polymerase I antibodies were found in the sera from healthy subjects. Individuals taking hydralazine, three of whom exhibited symptoms of drug-induced lupus, had barely detectable levels of the antibodies. Immunoglobulins obtained from sera containing anti-RNA polymerase I antibodies, as determined by the radioimmunoassay, could inhibit RNA polymerase I activity in vitro. Sera from patients with systemic lupus erythematosus contained immunoglobulins directed against the polymerase I-associated polypeptide of M[r] 65,000 as well as against the polypeptides of M[r] 120,000 or M[r] 25,000, or both. Sera from individuals with rheumatoid arthritis reacted with the polypeptide of M[r] 65,000 only. The antibodies in the sera of patients with mixed connective tissue disease were directed against the M[r] 42,000 polypeptide or a combination of the M[r] 65,000, 42,000, and 25,000 polypeptides. These data suggest that the production of anti-RNA polymerase I antibodies may be a unique characteristic of individuals with rheumatic autoimmune diseases and that the production of antibodies against specific polypeptides of RNA polymerase I may be indicative of the particular class of disease.