|
|
Ann Rheum Dis. 2004 September; 63(9): 1079–1084. doi: 10.1136/ard.2003.019877. | PMCID: PMC1755115 |
Diagnostic and clinical value of anti-cyclic citrullinated peptide antibodies compared with rheumatoid factor isotypes in rheumatoid arthritis I Vallbracht, J Rieber, M Oppermann, F Forger, U Siebert, and K Helmke Krankenhaus München-Bogenhausen, Clinical Immunology/Rheumatology, Teaching Hospital of the University of Munich, Munich, Germany. Objective: To assess the additional diagnostic and clinical value of the second test generation of anti-cyclic citrullinated peptide antibodies (CCP2) compared with rheumatoid factor isotypes (IgG-RF, IgA-RF, IgM-RF) in patients with rheumatoid arthritis. Methods: This was a prospective study on 715 patients: rheumatoid arthritis (n = 295), degenerative or other inflammatory joint disease (n = 163), connective tissue disease or vasculitis (n = 103), and healthy controls (n = 154). Sera from each subject were tested for CCP2 and RF isotypes by enzyme linked immunosorbent assay (ELISA). Agreement with clinical indices such as disease activity, joint destruction, disease duration, and other laboratory tests was assessed. Sensitivity and specificity of the tests were evaluated taking the clinical diagnosis as the gold standard. Results: Highest sensitivity was found for IgM-RF (66.4%) and CCP (64.4%). Highest specificity was achieved by CCP (97.1%) and IgG-RF (91.0%). In rheumatoid patients with high disease activity or severe joint damage, CCP was more often present (81.4% and 83.6%) than all RF isotypes. Of special diagnostic value was the detection of positive CCP in 34.5% of all patients with rheumatoid arthritis when all measured RF isotypes (IgG-RF, IgA-RF, and IgM- RF) were negative. Conclusions: As a screening method for rheumatoid arthritis the IgM-RF and the CCP assays are superior to other RF isotypes. Positivity in the highly specific CCP ELISA supports the diagnosis of rheumatoid arthritis. CCP proved to be a powerful diagnostic tool, especially in ambiguous cases or RF negative patients with rheumatoid arthritis. The Full Text of this article is available as a PDF (81K). These references are in PubMed. This may not be the complete list of references from this article. - Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988 Mar;31(3):315–324. [PubMed]
- Egeland T, Munthe E. The role of the laboratory in rheumatology. Rheumatoid factors. Clin Rheum Dis. 1983 Apr;9(1):135–160. [PubMed]
- Thorsteinsson J, Björnsson OJ, Kolbeinsson A, Allander E, Sigfússon N, Olafsson O. A population study of rheumatoid factor in Iceland. A 5-year follow-up of 50 women with rheumatoid factor (RF). Ann Clin Res. 1975 Jun;7(3):183–194. [PubMed]
- Mikkelsen WM, Dodge HJ, Duff IF, Kato H. Estimates of the prevalence of rheumatic diseases in the population of Tecumseh, Michigan, 1959-60. J Chronic Dis. 1967 Jun;20(6):351–369. [PubMed]
- Sebbag M, Simon M, Vincent C, Masson-Bessière C, Girbal E, Durieux JJ, Serre G. The antiperinuclear factor and the so-called antikeratin antibodies are the same rheumatoid arthritis-specific autoantibodies. J Clin Invest. 1995 Jun;95(6):2672–2679. [PubMed]
- NIENHUIS RL, MANDEMA E. A NEW SERUM FACTOR IN PATIENTS WITH RHEUMATOID ARTHRITIS; THE ANTIPERINUCLEAR FACTOR. Ann Rheum Dis. 1964 Jul;23:302–305. [PubMed]
- Mediwake R, Isenberg DA, Schellekens GA, van Venrooij WJ. Use of anti-citrullinated peptide and anti-RA33 antibodies in distinguishing erosive arthritis in patients with systemic lupus erythematosus and rheumatoid arthritis. Ann Rheum Dis. 2001 Jan;60(1):67–68. [PubMed]
- Eberhardt KB, Truedsson L, Pettersson H, Svensson B, Stigsson L, Eberhardt JL, Wollheim FA. Disease activity and joint damage progression in early rheumatoid arthritis: relation to IgG, IgA, and IgM rheumatoid factor. Ann Rheum Dis. 1990 Nov;49(11):906–909. [PubMed]
- Winska Wiloch H, Thompson K, Young A, Corbett M, Shipley M, Hay F. IgA and IgM rheumatoid factors as markers of later erosive changes in rheumatoid arthritis (RA). Scand J Rheumatol Suppl. 1988;75:238–243. [PubMed]
- Schellekens GA, de Jong BA, van den Hoogen FH, van de Putte LB, van Venrooij WJ. Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies. J Clin Invest. 1998 Jan 1;101(1):273–281. [PubMed]
- van Jaarsveld CH, ter Borg EJ, Jacobs JW, Schellekens GA, Gmelig-Meyling FH, van Booma-Frankfort C, de Jong BA, van Venrooij WJ, Bijlsma JW. The prognostic value of the antiperinuclear factor, anti-citrullinated peptide antibodies and rheumatoid factor in early rheumatoid arthritis. Clin Exp Rheumatol. 1999 Nov–Dec;17(6):689–697. [PubMed]
- Schellekens GA, Visser H, de Jong BA, van den Hoogen FH, Hazes JM, Breedveld FC, van Venrooij WJ. The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide. Arthritis Rheum. 2000 Jan;43(1):155–163. [PubMed]
- Meyer O, Labarre C, Dougados M, Goupille Ph, Cantagrel A, Dubois A, Nicaise-Roland P, Sibilia J, Combe B. Anticitrullinated protein/peptide antibody assays in early rheumatoid arthritis for predicting five year radiographic damage. Ann Rheum Dis. 2003 Feb;62(2):120–126. [PubMed]
- Kroot EJ, de Jong BA, van Leeuwen MA, Swinkels H, van den Hoogen FH, van't Hof M, van de Putte LB, van Rijswijk MH, van Venrooij WJ, van Riel PL. The prognostic value of anti-cyclic citrullinated peptide antibody in patients with recent-onset rheumatoid arthritis. Arthritis Rheum. 2000 Aug;43(8):1831–1835. [PubMed]
- Visser Henk, le Cessie Saskia, Vos Koen, Breedveld Ferdinand C, Hazes Johanna M W. How to diagnose rheumatoid arthritis early: a prediction model for persistent (erosive) arthritis. Arthritis Rheum. 2002 Feb;46(2):357–365. [PubMed]
- Girbal-Neuhauser E, Durieux JJ, Arnaud M, Dalbon P, Sebbag M, Vincent C, Simon M, Senshu T, Masson-Bessière C, Jolivet-Reynaud C, Jolivet M, Serre G. The epitopes targeted by the rheumatoid arthritis-associated antifilaggrin autoantibodies are posttranslationally generated on various sites of (pro)filaggrin by deimination of arginine residues. J Immunol. 1999 Jan 1;162(1):585–594. [PubMed]
- Jonsson T, Arnason JA, Valdimarsson H. Enzyme-linked immunosorbent assay (ELISA) screening test for detection of rheumatoid factor. Rheumatol Int. 1986;6(5):199–204. [PubMed]
- Ekdahl C, Eberhardt K, Andersson SI, Svensson B. Assessing disability in patients with rheumatoid arthritis. Use of a Swedish version of the Stanford Health Assessment Questionnaire. Scand J Rheumatol. 1988;17(4):263–271. [PubMed]
- Felson DT, Anderson JJ, Boers M, Bombardier C, Chernoff M, Fried B, Furst D, Goldsmith C, Kieszak S, Lightfoot R, et al. The American College of Rheumatology preliminary core set of disease activity measures for rheumatoid arthritis clinical trials. The Committee on Outcome Measures in Rheumatoid Arthritis Clinical Trials. Arthritis Rheum. 1993 Jun;36(6):729–740. [PubMed]
- Larsen A, Dale K, Eek M. Radiographic evaluation of rheumatoid arthritis and related conditions by standard reference films. Acta Radiol Diagn (Stockh). 1977 Jul;18(4):481–491. [PubMed]
- Goldbach-Mansky R, Lee J, McCoy A, Hoxworth J, Yarboro C, Smolen JS, Steiner G, Rosen A, Zhang C, Ménard HA, Zhou ZJ, Palosuo T, Van Venrooij WJ, Wilder RL, Klippel JH, Schumacher HR, Jr, El-Gabalawy HS. Rheumatoid arthritis associated autoantibodies in patients with synovitis of recent onset. Arthritis Res. 2000;2(3):236–243. [PubMed]
- Egsmose C, Lund B, Borg G, Pettersson H, Berg E, Brodin U, Trang L. Patients with rheumatoid arthritis benefit from early 2nd line therapy: 5 year followup of a prospective double blind placebo controlled study. J Rheumatol. 1995 Dec;22(12):2208–2213. [PubMed]
- van der Heide A, Jacobs JW, Bijlsma JW, Heurkens AH, van Booma-Frankfort C, van der Veen MJ, Haanen HC, Hofman DM, van Albada-Kuipers GA, ter Borg EJ, Brus HL, Dinant HJ, Kruize AA, Schenk Y. The effectiveness of early treatment with "second-line" antirheumatic drugs. A randomized, controlled trial. Ann Intern Med. 1996 Apr 15;124(8):699–707. [PubMed]
- Symmons DP, Jones MA, Scott DL, Prior P. Longterm mortality outcome in patients with rheumatoid arthritis: early presenters continue to do well. J Rheumatol. 1998 Jun;25(6):1072–1077. [PubMed]
- Anderson JJ, Wells G, Verhoeven AC, Felson DT. Factors predicting response to treatment in rheumatoid arthritis: the importance of disease duration. Arthritis Rheum. 2000 Jan;43(1):22–29. [PubMed]
- Boers M, Verhoeven AC, Markusse HM, van de Laar MA, Westhovens R, van Denderen JC, van Zeben D, Dijkmans BA, Peeters AJ, Jacobs P, van den Brink HR, Schouten HJ, van der Heijde DM, Boonen A, van der Linden S. Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis. Lancet. 1997 Aug 2;350(9074):309–318. [PubMed]
- Jansen Annemarie L M A, van der Horst-Bruinsma Irene, van Schaardenburg Dirkjan, van de Stadt Rob J, de Koning Margret H M T, Dijkmans Ben A C. Rheumatoid factor and antibodies to cyclic citrullinated Peptide differentiate rheumatoid arthritis from undifferentiated polyarthritis in patients with early arthritis. J Rheumatol. 2002 Oct;29(10):2074–2076. [PubMed]
- Lee DM, Schur PH. Clinical utility of the anti-CCP assay in patients with rheumatic diseases. Ann Rheum Dis. 2003 Sep;62(9):870–874. [PubMed]
- Suzuki K, Sawada T, Murakami A, Matsui T, Tohma S, Nakazono K, Takemura M, Takasaki Y, Mimori T, Yamamoto K. High diagnostic performance of ELISA detection of antibodies to citrullinated antigens in rheumatoid arthritis. Scand J Rheumatol. 2003;32(4):197–204. [PubMed]
- Pinheiro Geraldo Castelar, Scheinberg Morton A, Aparecida da Silva Miriam, Maciel Suely. Anti-cyclic citrullinated peptide antibodies in advanced rheumatoid arthritis. Ann Intern Med. 2003 Aug 5;139(3):234–235. [PubMed]
- van Venrooij WJ, Hazes JM, Visser H. Anticitrullinated protein/peptide antibody and its role in the diagnosis and prognosis of early rheumatoid arthritis. Neth J Med. 2002 Nov;60(10):383–388. [PubMed]
- Vasishta Anil. Diagnosing early-onset rheumatoid arthritis: the role of anti-CCP antibodies. Am Clin Lab. 2002 Aug–Sep;21(7):34–36. [PubMed]
- Zeng Xiaofeng, Ai Maixing, Tian Xinping, Gan Xiaodan, Shi Yanping, Song Qinfang, Tang Fulin. Diagnostic value of anti-cyclic citrullinated Peptide antibody in patients with rheumatoid arthritis. J Rheumatol. 2003 Jul;30(7):1451–1455. [PubMed]
- Rantapää-Dahlqvist Solbritt, de Jong Ben A W, Berglin Ewa, Hallmans Göran, Wadell Göran, Stenlund Hans, Sundin Ulf, van Venrooij Walther J. Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Arthritis Rheum. 2003 Oct;48(10):2741–2749. [PubMed]
- Bas S, Genevay S, Meyer O, Gabay C. Anti-cyclic citrullinated peptide antibodies, IgM and IgA rheumatoid factors in the diagnosis and prognosis of rheumatoid arthritis. Rheumatology (Oxford). 2003 May;42(5):677–680. [PubMed]
- Vencovský J, Machácek S, Sedová L, Kafková J, Gatterová J, Pesáková V, Růzicková S. Autoantibodies can be prognostic markers of an erosive disease in early rheumatoid arthritis. Ann Rheum Dis. 2003 May;62(5):427–430. [PubMed]
- Paimela L, Palosuo T, Aho K, Lukka M, Kurki P, Leirisalo-Repo M, von Essen R. Association of autoantibodies to filaggrin with an active disease in early rheumatoid arthritis. Ann Rheum Dis. 2001 Jan;60(1):32–35. [PubMed]
- Vittecoq O, Pouplin S, Krzanowska K, Jouen-Beades F, Menard JF, Gayet A, Daragon A, Tron F, Le Loet X. Rheumatoid factor is the strongest predictor of radiological progression of rheumatoid arthritis in a three-year prospective study in community-recruited patients. Rheumatology (Oxford). 2003 Aug;42(8):939–946. [PubMed]
|
This article has been 