Open Journal of Rheumatology and Autoimmune Diseases, 2013, 3, 113-118 http://dx.doi.org/10.4236/ojra.2013.32017 Published Online May 2013 (http://www.scirp.org/journal/ojra) 113 Associations with Organ Involvement and Autoantibodies in Systemic Sclerosis: Results from the Canadian Scleroderma Research Group (CSRG) * Vikram Tangri 1 , Carly Hewson 1 , Murray Baron 2 , A. Bonner 3 , Marvin Fritzler 4 , Janet E. Pope 1 1 University of Western Ontario, London, Canada; 2 McGill University, Montreal, Canada; 3 McMaster University, Hamilton, Canada; 4 University of Calgary, Calgary, Canada. Email: janet.pope@sjhc.london.on.ca Received March 6 th , 2013; revised April 7 th , 2013; accepted April 14 th , 2013 Copyright © 2013 Vikram Tangri et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. ABSTRACT Objective: Serum from SSc patients was analyzed centrally to determine ANA patterns and extractable nuclear anti- gens (ENAs) between lcSSc and dcSSc and associations with organ involvement. Methods: 1145 SSc patients had ANA and ENA analyzed by indirect immunofluorescence on HEp-2 substrate at a screening serum dilution of 1/160. Most ENA antibodies [Sm. U1-RNP, Ro52, SS-A/Ro60, topoisomeraseI (Topo1), SS-B/La, chromatin, ribosomal P and Jo1] were measured by laser bead immunoassay; and RNA polymerase III (RNAP) by ELISA. Results: ANA was posi- tive in 95% (same in lcSSc, and dcSSc). Centromere pattern was present in 34%, speckled 22%, nucleolar 18%, homo- geneous and speckled (H&S) 16%, multiple nuclear dots 6%. Anti-centromere Ab (ACA) occurred in 46% of lcSSc and 11% of dcSSc (P = 0.0001). ENAs that differed between lcSSc and dcSSc subsets were Topo1 (OR 2.4, P = 0.0001) and RNAP (OR 5.6, P < 0.0001) more common in dcSSc. Overall, 15% had positive Topo1; usually with a H&S pattern (67%); Topo1 was associated with ILD on CXR (OR 2.3; 95% CI 1.5 - 3.5) and HRCT (OR 3.8; 95% CI 1.8 - 8.2). RNAP occurred in 18.5% (35.4% in dcSSc vs. 8.9% in lcSSc). Scleroderma renal crisis (SRC) was 13 times more likely if RNAP positive; P = 0.0001. ACA was only weakly associated with sPAP > 50 mmHg (OR 1.8; 95%CI 1.1 - 3.0). Conclusion: ANA homogeneous pattern alone is rare in SSc; ACA was significantly more common in lcSSc. Many ENAs are equal in lcSSc and dcSSc except RNAP and Topo1. RNAP has the highest OR of SRC. Topo1 is less strongly associated with ILD. Abstract word count: 249, Body word count 1246, Figures 2, Tables 2. Key Messages: 1) 95% of SSc has a positive ANA and ANA patterns in SSc include centromere, nucleolar, and homogeneous and speckled to- gether; 2) Most ENAs are equal in both dcSSc and lcSSc except anti RNA polymerase III and topoisomerase I; 3) RNA polymerase III has the highest association (odds ratio) with scleroderma renal crisis, topoisomerase I is associated with interstitial lung disease; whereas anticentromere was not associated with elevated pulmonary arterial pressures on echo- cardiogram. Keywords: Scleroderma; SSc; Systemic Sclerosis; Antibodies; Anticentromere; Topoisomerase I; RNA Polymerase III; Organ Involvement; Scleroderma Renal Crisis; Pulmonary Fibrosis; ILD; ANA; Pulmonary Hypertension 1. Introduction Systemic Sclerosis (SSc) is an autoimmune disorder cau- sing various clinical manifestations related to skin fibro- sis and internal organ dysfunction. Limited cutaneous sys- temic sclerosis (lcSSc) primarily affects the skin of the fingers and hands, while diffuse cutaneous systemic scle- rosis (dcSSc) is known to affect skin tissue and organs more extensively [1]. LcSSc is defined as skin involve- ment distal to the elbows/knees but may still affect the face and neck; whereas dcSSc involves skin that is also proximal to the elbows and/or knees or also truncal [1]. * CSRG (Canadian Scleroderma Research Group) is: J. Pope, London, Ontario; M. Baron, Montreal, Quebec; J. Markland, Saskatoon, Sas- katchewan; D. Robinson, Winnipeg, Manitoba; N. Jones, Edmonton, Alberta; N. Khalidi, Hamilton, Ontario; P. Docherty, Moncton, New Brunswick; E. Kaminska, Hamilton, Ontario; A. Masetto, Sherbrooke, Quebec; E. Sutton, Halifax, Nova Scotia; J-P. Mathieu, Montreal, Quebec; M. Hudson, Montreal, Quebec; S. Ligier, Montreal, Quebec; T. Grodzicky, Montreal, Quebec; S. LeClercq, Calgary, Alberta; C. Thorne, Newmarket, Ontario; G. Gyger, Montreal, Quebec; D. Smith, Ottawa, Ontario; M. Fritzler, Advanced Diagnostics Laboratory, Cal- gary, Alberta. The presence of autoantibodies can be associated with disease pathology and progression. Anti nuclear antibo- Copyright © 2013 SciRes. OJRA