To determine the clinical significance of anti-RNA polymerase III antibody in systemic sclerosis (SSc).

A point prevalence study of autoantibody to RNA polymerase III and longitudinal examination of its clinical significance in patients with SSc and in controls.

University medical center rheumatology practice.

Two hundred fifty-two consecutive new patients with SSc and 170 controls (150 patients with other connective tissue diseases and 20 normal volunteers).

The presence of anti-RNA polymerase III antibody was determined by immunoprecipitation, immunoblotting, and immunodepletion studies.

Serum specimens from 57 of the 252 patients with SSc (23%; 95% CI, 18% to 28%) reacted with RNA polymerase III, compared with none of the specimens from 170 controls (0%; 95% CI, 0% to 2%). In 40 of these 57 specimens, immunoprecipitation studies also showed the presence of RNA polymerase I or II, or both. Anti-RNA polymerase III antibody was detected in sera from 50 of the 111 patients (45%) who had SSc with diffuse cutaneous involvement (dcSSc), 7 of 114 patients (6%) who had SSc with limited cutaneous involvement, and none of 27 patients with an SSc overlap syndrome (P < 0.001). Among patients with dcSSc, anti-RNA polymerase III antibody was more common than antitopoisomerase I antibody (45% compared with 27%; P = 0.008). Patients with anti-RNA polymerase III antibody had a statistically significant higher mean maximum skin thickness score but statistically significant lower frequencies of telangiectasias, inflammatory myopathy, restrictive lung disease, and serious cardiac abnormalities than did patients with antitopoisomerase I antibody.

Anti-RNA polymerase III antibody is a new marker autoantibody for many patients who have SSc with diffuse or extensive cutaneous involvement.