title: Brief Report: Anti-RNPC-3 Antibodies As a Marker of Cancer-Associated Scleroderma.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Ami A
authors.initials: AA
authors.lastname: Shah
authors.affiliation: Harvard University and Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Cambridge, Massachusetts, and Howard Hughes Medical Institute and Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: George
authors.initials: G
authors.lastname: Xu
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Antony
authors.initials: A
authors.lastname: Rosen
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Laura K
authors.initials: LK
authors.lastname: Hummers
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Fredrick M
authors.initials: FM
authors.lastname: Wigley
authors.affiliation: Howard Hughes Medical Institute, Brigham and Women's Hospital, and Harvard University Medical School, Boston, Massachusetts.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Elledge
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Livia
authors.initials: L
authors.lastname: Casciola-Rosen
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood* / Q000150:complications / Q000276:immunology; D009687:Nuclear Proteins / Q000276:immunology*; D016601:RNA-Binding Proteins / Q000276:immunology*; D012595:Scleroderma, Systemic / Q000097:blood* / Q000276:immunology
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; C498172:RNPC3 protein, human