by Solid organ malignancies include breast, lung, colorectal, genitourinary and reproductive tract malignancies. 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%, em P /em 0.0001), joint contractures (73.9% vs. 30.1%, em P /em 0.0001), greater highest-recorded modified Rodnan skin score (20.6 12.4 vs. 10.1 7.9, em P /em 0.0001), synovitis (31.9% vs. 19.9%, em P /em = 0.03), myositis (2.9% vs. 0.5%, em P /em = 0.05), systemic hypertension (59.4% vs. 39.7%, em P /em = 0.002), renal crisis (24.6% vs. 1.8%, em P /em 0.0001) and malignancy diagnosed within 5 years of onset of SSc skin disease (13.3% vs. 3.9%, em P /em = 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, em P /em = 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, em P /em 0.0001; PPV 75.4%, NPV 20.9%), joint contractures (OR 2.5, 95% CI 1.2 to 5.3, em P /em = 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, em P /em = 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 SBC-110736 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. Introduction Systemic sclerosis (SSc) is a multisystem autoimmune disease characterized by vasculopathy and fibrosis [1]. The various manifestations of SSc in affected individuals evolve over time and range from digital ischemia and ulcers to potentially life-threatening renal crisis, interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH). This heterogeneity of clinical manifestations in SSc has led to efforts to find markers that enable identification of patients most at risk of involvement of particular organ systems, who would benefit from more frequent and organ-specific monitoring. Antibodies to RNA polymerase III (anti-RNAP), detected by immunoprecipitation, were first shown to have specificity for the diagnosis of SSc in the early 1990s [2]. More recently, through the availability of commercial ELISAs, various clinical correlates of anti-RNAP in SSc have been described [3]. Whilst these antibodies are currently thought not SPRY4 to play a pathogenic role, they have prognostic significance. Anti-RNAP appear early in the course of SBC-110736 SSc, and, although there is considerable intra-patient and inter-patient variability in antibody titers over time, actual levels SBC-110736 do not correlate with disease outcome [4]. A baseline measurement is therefore often sufficient. The reported frequency of anti-RNAP in various SSc cohorts ranges from 4 to 9.4% in French SSc patients [5-7], to 12% in English SSc patients [8], 6% in Japanese SSc patients [9], 19.4% in Canadian SSc patients [10] and 25% in American SSc patients [7] SBC-110736 Racial and genetic variations are hypothesized to account for these differences. Previously reported associations of anti-RNAP include diffuse cutaneous disease, higher maximum skin thickness score, tendon friction rubs and renal crisis [2,6,8,10-13]. Two recent studies have reported a close temporal association between the onset of SSc and diagnosis of cancer among SSc patients with anti-RNAP [14,15]. This association, however, is yet to be confirmed and quantified in large prospective studies. In the present study, our objective was to determine the prevalence of anti-RNAP in a large Australian cohort of patients with SSc. We sought to confirm and quantify previously described associations and to define.
