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

Arthritis Rheumatol. 2017 Jun;69(6):1306-1312. doi: 10.1002/art.40065.

Abstract

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.

Publication types

  • Validation Study

MeSH terms

  • Adult
  • Autoantibodies / blood*
  • Autoantibodies / immunology
  • Biomarkers / blood
  • Female
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Neoplasms / blood*
  • Neoplasms / complications
  • Neoplasms / immunology
  • Nuclear Proteins / immunology*
  • RNA-Binding Proteins / immunology*
  • Scleroderma, Systemic / blood*
  • Scleroderma, Systemic / immunology

Substances

  • Autoantibodies
  • Biomarkers
  • Nuclear Proteins
  • RNA-Binding Proteins
  • RNPC3 protein, human