A comparison of the frequency of antibodies to cyclic citrullinated peptides using a third generation anti-CCP assay (CCP3) in systemic sclerosis, primary biliary cirrhosis and rheumatoid arthritis |
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Authors: | Mittermayer Santiago Murray Baron Kiyomitsu Miyachi Marvin J. Fritzler M. Abu-Hakima S. Leclercq M. Bell M. Hudson J-P. Mathieu S. Taillefer N. Jones P. Docherty M. Khraishi J. Markland J. Pope D. Robinson D. Smith E. Sutton |
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Affiliation: | (1) Servico de Reumatologia do Hospital do Santa Izabel, Escola Bahiana de Medicina e Saude Publica, Salvador, Brazil;(2) Division of Rheumatology, Jewish General Hospital, McGill University, Montréal, PQ, Canada;(3) First Diagnostic Division, Health Sciences Research Institute, Yokohama, Japan;(4) Faculty of Medicine, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB, T2N 4N1, Canada;(5) Canadian Scleroderma Research Group, Calgary, AB, Canada;(6) Canadian Scleroderma Research Group, Toronto, ON, Canada;(7) Canadian Scleroderma Research Group, Montreal, PQ, Canada;(8) Canadian Scleroderma Research Group, Edmonton, AB, Canada;(9) Canadian Scleroderma Research Group, Moncton, NB, Canada;(10) Canadian Scleroderma Research Group, St John’s, NL, Canada;(11) Canadian Scleroderma Research Group, Saskatoon, SK, Canada;(12) Canadian Scleroderma Research Group, London, ON, Canada;(13) Canadian Scleroderma Research Group, Winnipeg, MB, Canada;(14) Canadian Scleroderma Research Group, Ottawa, ON, Canada;(15) Canadian Scleroderma Research Group, Halifax, NS, Canada |
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Abstract: | The objective was to investigate the frequency of anti-cyclic citrullinated peptides (CCP) antibodies in systemic sclerosis (SSc) and primary biliary cirrhosis (PBC), utilizing a new “third generation” anti-CCP ELISA (anti-CCP3) kit and a conventional anti-CCP2 assay. Patients with PBC, SSc, RA, and normal controls were included in the study. Serum samples were screened for autoantibodies by indirect immunofluorescence (IIF), antibodies to CCP by a second- and third-generation ELISA, antibodies to “scleroderma” antigens (CENP B, Scl-70, PM/Scl and fibrillarin—Scl-34) by a line immunoassay (LIA), and IgM RF by ELISA. The frequency of anti-CCP2 antibodies in SSc and PBC samples was 14.8% (11/74) and 6.2% (5/80), respectively, and the frequency of anti-CCP3 antibodies in SSc was 13.5% (10/74) and in PBC was 3.7% (3/80). By comparison, in the RA group the frequency of anti-CCP3 and anti-CCP2 antibodies was 79.1% (38/48) and 77% (37/48), respectively. Anti-CCP3 ELISA had a sensitivity, specificity, and positive and negative likelihood ratios (LR) of 79% (95% confidence interval [CI] = 64–89%), 93% (95% CI = 88–96%), 11.8 (95% CI = 6.8–20.3), and 0.22 (95% CI = 0.12–0.38), respectively. By comparison, the anti-CCP2 assay had a sensitivity, specificity, and positive and negative LRs of 77% (95% CI = 62–87), 90% (95% CI = 85–94), 8.3 (95% CI = 5.2–13.2), and 0.25 (95% CI = 0.15–0.42), respectively. In patients with SSc, there was an association of anti-CCP2 antibodies with the presence of arthritis, but there was no association of anti-CCP2 or anti-CCP3 with anti-CENP B, anti-Scl 70, or RF. This study confirmed the high specificity and sensitivity of both anti-CCP assays for the diagnosis of RA. The presence of anti-CCP antibodies in SSc was only correlated with the presence of arthritis. |
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Keywords: | Autoantibodies Cyclic citrullinated peptide Primary biliary cirrhosis Rheumatoid arthritis Sensitivity Specificity Systemic sclerosis |
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