Clinical significance of anti-RNA polymerase III antibodies in a cohort of patients from the australian scleroderma screening program (ASSP) database.

Abstract

Purpose: Anti-RNA polymerase III antibodies (anti-RNAP Abs), detectable in up to 25% of patients with systemic sclerosis (SSc), may define a novel subset of patients with severe cutaneous disease and an increased risk of renal hypertensive crisis. This is the first time the clinical associations of this Ab have been examined in an Australian population. We examined the prevalence and clinical variables associated with anti-RNAP Abs in a cohort of patients from the Australian Scleroderma Screening Program (ASSP) Database, a national prospective on-line electronic registry of clinical, laboratory and investigational parameters related to SSc and MCTD. Method(s): Review of patients from the ASSP Database tested for anti-RNAP Abs, since 2007. Anti-RNAP was measured using a commercially available ELISA kit (Quanta Lite RNA Pol III-Integrated Sciences) and compared with anti-Scl70 Ab. Result(s): Of the 714 patients on the ASSP database, 219 were tested for anti-RNAP Abs and 36 (16%) were positive. These patients were more likely than RNAP negative patients to have diffuse (dcSSc) than limited (lcSSc) cutaneous disease (72% cf 28% p<0.001), higher mean Rodnan skin scores (20 cf 10, p<0.001), more joint contractures (66% cf 22%, p<0.001), more hypertension (56% cf 32%, p<0.01), and more suspected or proven renal crisis (18% cf 2%, p<0.001). In the subset of patients with dcSS, anti-RNAP Abs were associated with higher mean skin scores (23 cf 18, p <0.05), joint contractures (81% cf 48%, p<0.05) and hypertension (54% cf 26%, p<0.05), suggesting additional risk beyond that seen in patients with dcSSc subtype alone. 215 of the 219 patients were also tested for anti-Scl70 Ab. 44(20%) were positive, 53% had dcSSc and 45% lcSSc. Anti-RNAP Ab positive patients compared to anti-Scl70 Ab positive patients had higher mean Rodnan skin scores (20 cf 14), more joint contractures (67% cf 45%), hypertension (56% cf 34%) and suspected or proven renal crisis (18% cf 2%). Only 1 patient was positive for both anti-RNAP and anti-Scl70 Ab. Conclusion(s): The ASSP Database results support findings from previous studies showing an association between RNAP Ab positivity and severe skin and renal disease. Our results suggest the risk is above that seen with diffuse disease subtype or anti-Scl-70 Ab alone. ELISA testing for anti-RNAP Abs may therefore be useful to predict those at risk of severe skin and renal disease.