Open Access Research article

Prevalence, correlates and clinical usefulness of antibodies to RNA polymerase III in systemic sclerosis: a cross-sectional analysis of data from an Australian cohort

Mandana Nikpour12*, Pravin Hissaria34, Jillian Byron5, Joanne Sahhar6, Maree Micallef2, William Paspaliaris7, Janet Roddy8, Peter Nash9, Alan Sturgess10, Susanna Proudman11 and Wendy Stevens2

Author affiliations

1 The University of Melbourne, Department of Medicine, St. Vincent's Hospital Melbourne, 41 Victoria Parade, Fitzroy, Victoria 3065, Australia

2 Department of Rheumatology, St. Vincent's Hospital Melbourne, 41 Victoria Parade, Fitzroy, Victoria 3065, Australia

3 Departments of Clinical Immunology and Immunopathology, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5000, Australia

4 Institute of Medical and Veterinary Science/SA Pathology, 72 King William Road, North Adelaide, South Australia 5000, Australia

5 Australian Scleroderma Interest Group Project Coordinator, Department of Rheumatology, St. Vincent's Hospital Melbourne, 41 Victoria Parade, Fitzroy, Victoria 3065, Australia

6 Department of Rheumatology, Monash Medical Centre, 246 Clayton Road, Clayton, Melbourne, Victoria 3168, Australia

7 Diagnostic Immunology Laboratory, St. Vincent's Hospital Melbourne, 41 Victoria Parade, Fitzroy, Victoria 3065, Australia

8 Department of Rheumatology, Royal Perth Hospital, Wellington Street (GPO Box X2213), Perth, Western Australia 6001, Australia

9 Sunshine Coast Rheumatology, PO Box 368, Maroochydore, Sunshine Coast, Queensland 4558, Australia

10 Department of Rheumatology, The St. George Hospital, Gray Street, Kogarah, New South Wales 2217, Australia

11 Department of Rheumatology, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5000, Australia

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Citation and License

Arthritis Research & Therapy 2011, 13:R211  doi:10.1186/ar3544

Published: 22 December 2011

Abstract

Introduction

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.