Brief Report: Anti–RNPC-3 Antibodies As a Marker of Cancer-Associated Scleroderma

Objective: Prior studies have demonstrated an increased risk of cancer-associated scleroderma in patients with anti–RNA polymerase III (anti–RNAP III) autoantibodies as well as in patients who are triple-negative for anticentromere (anti-CENP), anti–topoisomerase I (anti–topo I), and anti–RNAP III (also known as anti-POL) autoantibodies (referred to as CTP negative). In a recent study of 16 CTP-negative scleroderma patients with coincident cancer, 25% of the patients were found to have autoantibodies to RNPC-3, a member of the minor spliceosome complex. This investigation was undertaken to validate the relationship between anti–RNPC-3 antibodies and cancer and examine the associated clinical phenotype in a large sample of scleroderma patients. Methods: Scleroderma patients with cancer were assayed for anti-CENP, anti–topo I, anti–RNAP III, and anti–RNPC-3 autoantibodies. Disease characteristics and the cancer–scleroderma interval were compared across autoantibody groups. The relationship between autoantibody status and cancer-associated scleroderma was assessed by logistic regression. Results: Of 318 patients with scleroderma and cancer, 70 (22.0%) were positive for anti–RNAP III, 54 (17.0%) were positive for anti–topo I, and 96 (30.2%) were positive for anti-CENP. Twelve patients (3.8% of the overall group or 12.2% of CTP-negative patients) were positive for anti–RNPC-3. Patients with anti–RNPC-3 had a short cancer–scleroderma interval (median 0.9 years). Relative to patients with anti-CENP, patients with anti–RNPC-3 and those with anti–RNAP III had a >4-fold increased risk of cancer within 2 years of scleroderma onset (for anti–RNPC-3–positive patients, odds ratio [OR] 4.3, 95% confidence interval [95% CI] 1.10–16.9 [P = 0.037]; for anti–RNAP III–positive patients, OR 4.49, 95% CI 1.98–10.2 [P < 0.001]). Patients with anti–RNPC-3 had severe restrictive lung disease, gastrointestinal disease, Raynaud's phenomenon, and myopathy. Conclusion: Anti–RNPC-3 autoantibodies, similar to anti–RNAP III autoantibodies, are associated with an increased risk of cancer at the onset of scleroderma. These data suggest the possibility of cancer-induced autoimmunity in this subset of patients with scleroderma.