title: Prevalence, correlates and clinical usefulness of antibodies to RNA polymerase III in systemic sclerosis: a cross-sectional analysis of data from an Australian cohort.
abstract: BACKGROUND
  The prevalence of antibodies to RNA polymerase III (anti-RNAP) differs among systemic sclerosis (SSc) cohorts worldwide. Previously reported associations of anti-RNAP include diffuse cutaneous disease, tendon friction rubs and renal crisis, with recent reports suggesting a close temporal association between malignancy and SSc disease onset among patients with anti-RNAP.
  
  
  METHODS
  Patients with SSc were tested for the presence of anti-RNAP at recruitment into the Australian Scleroderma Cohort Study. We used univariate and multivariable methods to identify and quantify clinical and laboratory correlates of anti-RNAP in SSc. Diagnostic testing procedures were used to determine the usefulness of these antibodies in estimating the likelihood of clinically important outcomes.
  
  
  RESULTS
  There were 451 patients with mean ± standard deviation age and disease duration at recruitment of 58.1 ± 12.4 and 11.6 ± 10.0 years, respectively; 151 (33.5%) patients were recruited within 5 years of diagnosis of SSc. Overall, 69 (15.3%) patients had anti-RNAP. Univariate associations of anti-RNAP were diffuse disease (75.4% vs. 20.9%, P < 0.0001), joint contractures (73.9% vs. 30.1%, P < 0.0001), greater highest-recorded modified Rodnan skin score (20.6 ± 12.4 vs. 10.1 ± 7.9, P < 0.0001), synovitis (31.9% vs. 19.9%, P = 0.03), myositis (2.9% vs. 0.5%, P = 0.05), systemic hypertension (59.4% vs. 39.7%, P = 0.002), renal crisis (24.6% vs. 1.8%, P < 0.0001) and malignancy diagnosed within 5 years of onset of SSc skin disease (13.3% vs. 3.9%, P = 0.01). In multiple regression analysis, after adjustment for other covariates, anti-RNAP were independently associated with renal crisis (odds ratio (OR) 3.8, 95% confidence interval (CI) 1.2 to 11.5, P = 0.02; positive predictive value (PPV) 24.6%, negative predictive value (NPV) 98.2%), diffuse disease (OR 6.4, 95% CI 2.9 to 13.8, P < 0.0001; PPV 75.4%, NPV 20.9%), joint contractures (OR 2.5, 95% CI 1.2 to 5.3, P = 0.02; PPV 73.9%, NPV 69.9%) and malignancy diagnosed within 5 years of onset of SSc skin disease (OR 4.2, 95% CI 1.3 to 13.4, P = 0.01; PPV 13.3%, NPV 96.1%).
  
  
  CONCLUSIONS
  Anti-RNAP status is a clinically useful prognostic marker in SSc and enables clinicians to identify patients at high risk of developing renal crisis, synovitis, myositis and joint contractures. Patients with anti-RNAP also have an increased risk of malignancy within a 5-year timeframe before or after onset of SSc skin changes.
authors.affiliation: The University of Melbourne, Department of Medicine, St, Vincent's Hospital Melbourne, 41 Victoria Parade, Fitzroy, Victoria 3065, Australia. mnikpour@medstv.unimelb.edu.au
authors.forename: Mandana
authors.initials: M
authors.lastname: Nikpour
authors.forename: Pravin
authors.initials: P
authors.lastname: Hissaria
authors.forename: Jillian
authors.initials: J
authors.lastname: Byron
authors.forename: Joanne
authors.initials: J
authors.lastname: Sahhar
authors.forename: Maree
authors.initials: M
authors.lastname: Micallef
authors.forename: William
authors.initials: W
authors.lastname: Paspaliaris
authors.forename: Janet
authors.initials: J
authors.lastname: Roddy
authors.forename: Peter
authors.initials: P
authors.lastname: Nash
authors.forename: Alan
authors.initials: A
authors.lastname: Sturgess
authors.forename: Susanna
authors.initials: S
authors.lastname: Proudman
authors.forename: Wendy
authors.initials: W
authors.lastname: Stevens
mesh_terms: D000368:Aged; D001315:Australia / Q000453:epidemiology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D015995:Prevalence; D012320:RNA Polymerase III / Q000276:immunology*; D018570:Risk Assessment; D012307:Risk Factors; D012595:Scleroderma, Systemic / Q000097:blood / Q000453:epidemiology / Q000276:immunology*; D012867:Skin / Q000276:immunology* / Q000473:pathology
chemical_list: D001323:Autoantibodies; D012320:RNA Polymerase III