Anti-RNPC3 Antibodies as a Marker of Cancer-Associated Scleroderma

Abstract

Introduction

Prior studies have demonstrated an increased risk of cancer-associated scleroderma in patients with RNA polymerase III (POL) autoantibodies and in patients negative for anti-centromere (CENP), anti-topoisomerase-1 (TOPO), and anti-POL antibodies (referred to as CENP/TOPO/POL (CTP)-Negative). In a recent study of 16 CTP-negative scleroderma patients with coincident cancer, we found that 25% had autoantibodies to RNPC3, a member of the minor spliceosome complex. In this investigation, we validated the relationship between anti-RNPC3 antibodies and cancer and examined the associated clinical phenotype in a large sample of scleroderma patients.

Methods

Scleroderma patients with cancer were assayed for CENP, TOPO, POL and RNPC3 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-POL, 54 (17.0%) for anti-TOPO, and 96 (30.2%) for anti-CENP. Twelve patients (3.8% of overall group or 12.2% of CTP-negatives) were positive for anti-RNPC3. Patients with anti-RNPC3 had a short cancer-scleroderma interval (median 0.9 years). Relative to patients with anti-CENP, patients with anti-RNPC3 (OR 4.3; 95%CI 1.10–16.9; p=0.037) and anti-POL (OR 4.49; 95%CI 1.98–10.2; p<0.001) had a >4-fold increased risk of cancer within 2 years of scleroderma onset. Patients with anti-RNPC3 had severe restrictive lung and gastrointestinal disease, Raynaud’s, and myopathy.

Conclusion

Anti-RNPC3 autoantibodies associate with an increased risk of cancer at scleroderma onset, similar to POL autoantibodies. These data suggest the possibility of cancer-induced autoimmunity in this scleroderma subset.