Autoantibody Reactive with RNA Polymerase III in Systemic Sclerosis

doi:10.1059/0003-4819-119-10-199311150-00007

Autoantibody Reactive with RNA Polymerase III in Systemic Sclerosis

From the University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Requests for Reprints: Thomas A. Medsger, Jr., MD, Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh School of Medicine, 985 Scaife Hall, Pittsburgh, PA 15261. Acknowledgments: The authors thank Drs. R. Kovelman and R. G. Roeder (Rockefeller University School of Medicine) for providing the partially purified RNA polymerase III; Dr. M. Schmidt (University of Pittsburgh School of Medicine) for providing HeLa S100 extracts and pVA I DNA template; Colleen Thomas, Claudia Conte, and Noreen Fertig for providing technical assistance; and Joan Neitznick and Roberta Shope for secretarial assistance. Grant Support: In part by The Arthritis Foundation, Western Pennsylvania Chapter (Shoemaker Fund), Pittsburgh, Pennsylvania; The Scleroderma Federation, New York, New York; The RGK Foundation, Austin, Texas; National Institutes of Health grant 5M01RR00056; and the Arthritis, Rheumatism and Aging Medical Information System (ARAMIS) National Institutes of Health grant AR21393.

Abstract

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

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

Setting: University medical center rheumatology practice.

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

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

Main Results: 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.

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