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Prevalence and predictive value of anti-cyclic citrullinated protein antibodies for future development of rheumatoid arthritis in early undifferentiated arthritis

  • Original Article
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Modern Rheumatology

Abstract

The aim of this study is to evaluate the prevalence and predictive value of anti-cyclic citrullinated protein (CCP) antibodies as a diagnostic marker for future development of rheumatoid arthritis (RA) in a cohort of patients presenting with undifferentiated arthritis (UA). The study comprised 69 patients (22 males and 47 females) presenting with UA, and 66 healthy subjects as control group. For all patients the following parameters were assessed: swollen joint count (SJC), tender joint count (TJC), and duration of morning stiffness in minutes. Baseline laboratory investigations included erythrocyte sedimentation rate (ESR) first hour, C-reactive protein (CRP), complete blood count, complete liver and kidney function tests, urine analysis, anti-nuclear antibodies, rheumatoid factor (RF), and anti-CCP antibodies. Positive correlations were observed between anti-CCP versus SJC, TJC (p = 0.001), duration of morning stiffness (p = 0.04), ESR first hour, and bone erosive changes (p = 0.001). Anti-CCP showed sensitivity of 57%, specificity of 37.9%, positive predictive value of 65.1%, and negative predictive value of 39.3%. Sensitivity and positive predictive values of anti-CCP are close to those observed for RF. In patients presenting with UA, anti-CCP antibodies may allow prediction of RA, thereby allowing early individualized therapeutic decisions.

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References

  1. van der Helm-van Mil AH, le Cessie S, van Dongen H, Breedveld FC, Toes RE, Huizinga TW. A prediction rule for disease outcome in patients with recent-onset undifferentiated arthritis: how to guide individual treatment decisions. Arthritis Rheum. 2007;56:433–40.

    Article  PubMed  Google Scholar 

  2. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988;313:15–24.

    Google Scholar 

  3. Harrison BJ, Symmons DP, Barrett EM, Silman AJ. The performance of the 1987 ARA classification criteria for rheumatoid arthritis in a population based cohort of patients with early inflammatory polyarthritis. American Rheumatism Association. J Rheumatol. 1998;25:2324–30.

    CAS  PubMed  Google Scholar 

  4. Huizinga TWJ, Machold KP, Breedveld FC, Lipsky PE, Smolen JS. Criteria for early rheumatoid arthritis: from Bayes’ law revisited to new thoughts on pathogenesis. Arthritis Rheum. 2002;46:1155–9.

    Article  PubMed  Google Scholar 

  5. Verpoort KN, van Dongen H, Allaart CF, Toes RE, Breedveld FC, Huizinga TW. Undifferentiated arthritis-disease course assessed in several inception cohorts. Clin Exp Rheumatol. 2004;22:S12–7.

    CAS  PubMed  Google Scholar 

  6. Van Gaalen FA, Linn-Rasker SP, van Venrooij WJ, et al. Autoantibodies to cyclic citrullinated peptides (CCP) predicts progression to rheumatoid arthritis in patients with undifferentiated arthritis: a prospective cohort study. Arthritis Rheum. 2004;50:709–15.

    Article  PubMed  Google Scholar 

  7. Vittecoq O, Incaurgarat B, Jouen-Beades F, et al. Autoantibodies recognizing citrullinated rat filaggrin in an ELISA using citrullinated and non-citrullinated recombinant proteins as antigens are highly diagnostic for rheumatoid arthritis. Clin Exp Immunol. 2004;135:173–80.

    Article  CAS  PubMed  Google Scholar 

  8. Combe B, Landewe R, Lukas C, et al. EULAR recommendations for the management of early arthritis: report of a task force of the European Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT)]. Ann Rheum Dis. 2007;66:34–5.

    Article  CAS  PubMed  Google Scholar 

  9. Avouac J, Gossec L, Dougados M. Diagnostic and predictive value of anti-cyclic citrullinated protein antibodies in rheumatoid arthritis: a systematic literature review. Ann Rheum Dis. 2006;65:845–51.

    Article  CAS  PubMed  Google Scholar 

  10. Emad Y, Ragab Y, Shaarawy A, Abou-Zeid A, Saad A, Fawzy M, et al. Can magnetic resonance imaging differentiate undifferentiated arthritis based on knee imaging? J Rheumatol. 2009;36:1963–70.

    Article  PubMed  Google Scholar 

  11. van der Helm-van Mil AH, Detert J, le Cessie S, Filer A, Bastian H, Burmester GR, et al. Validation of a prediction rule for disease outcome in patients with recent-onset undifferentiated arthritis: moving toward individualized treatment decision-making. Arthritis Rheum. 2008;58:2241–7.

    Article  PubMed  Google Scholar 

  12. Lard LR, Visser H, Speyer I, vander Horst-Bruinsma IE, Zwinderman AH, Breedveld FC, et al. Early versus delayed treatment in patients with recent-onset rheumatoid arthritis: comparison of two cohorts who received different treatment strategies. Am J Med. 2001;111:446–51.

    Article  CAS  PubMed  Google Scholar 

  13. van der Heide A, Jacobs JW, Bijlsma JW, Heurkens AH, van Booma-Frankfort C, van der Veen MJ, et al. The effectiveness of early treatment with antirheumatic drugs. A randomized, controlled trial. Ann Intern Med. 1996;124:699–707.

    PubMed  Google Scholar 

  14. Wassenberg S, Rau R. Radiographic healing with sustained clinical remission in a patient with rheumatoid arthritis receiving methotrexate monotherapy. Arthritis Rheum. 2002;46:2804–7.

    Article  PubMed  Google Scholar 

  15. Quinn MA, Green MJ, Marzo-Ortega H, Proudman S, Karim Z, Wakefield RJ, et al. Prognostic factors in a large cohort of patients with early undifferentiated inflammatory arthritis after application of a structured management protocol. Arthritis Rheum. 2003;48:3039–45.

    Article  PubMed  Google Scholar 

  16. van Jaarsveld CH, ter Borg EJ, Jacobs JW, Schellekens GA, Gmelig-Meyling FH, van Booma-Frankfort C, et al. The prognostic value of the antiperinuclear factor, anti-citrullinated peptide antibodies and rheumatoid factor in early rheumatoid arthritis. Clin Exp Rheumatol. 1999;17:689–97.

    PubMed  Google Scholar 

  17. Meyer O, Labarre C, Dougados M, Goupille P, Cantagrel A, Dubois A, et al. Anticitrullinated protein/peptide antibody assays in early rheumatoid arthritis for predicting five year radiographic damage. Ann Rheum Dis. 2003;62:120–6.

    Article  CAS  PubMed  Google Scholar 

  18. Vencovský J, Machácek S, Sedová L, Kafková J, Gatterová J, Pesáková V, et al. Autoantibodies can be prognostic markers of an erosive disease in early rheumatoid arthritis. Ann Rheum Dis. 2003;62:427–30.

    Article  PubMed  Google Scholar 

  19. Saraux A, Berthelot JM, Devauchelle V, Bendaoud B, Chalès G, Le Henaff C, et al. Value of antibodies to citrulline-containing peptides for diagnosing early rheumatoid arthritis. J Rheumatol. 2003;30:2535–9.

    CAS  PubMed  Google Scholar 

  20. Lindqvist E, Eberhardt K, Bendtzen K, Heinegard D, Saxne T. Prognostic laboratory markers of joint damage in rheumatoid arthritis. Ann Rheum Dis. 2005;64:196–201.

    Article  CAS  PubMed  Google Scholar 

  21. 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;43:1831–5.

    Google Scholar 

  22. Visser H, Le Cessie S, Vos K, Breedveld FC, Hazes JM. How to diagnose rheumatoid arthritis early? A prediction model for persistent (erosive) arthritis. Arthritis Rheum. 2002;46:357–65.

    Article  PubMed  Google Scholar 

  23. Pruijn GJM, Vossenaar1 ER, Drijfhout JW, van Venrooij1 WJ, Zendman AJW. Anti-CCP antibody detection facilitates early diagnosis and prognosis of rheumatoid arthritis. Curr Rheumatol Rev. 2005;1:1–7.

    Google Scholar 

  24. Nielen MM, van Schaardenburg D, Reesink HW, van de Stadt RJ, van der Horst-Bruinsma IE, de Koning MH, et al. Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. Arthritis Rheum. 2004;50:380–3.

    Article  PubMed  Google Scholar 

  25. Rantapää-Dahlqvist S, de Jong BA, Berglin E, Hallmans G, Wadell G, Stenlund H, et al. Antibodies against citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Arthritis Rheum. 2003;48:2741–9.

    Article  PubMed  Google Scholar 

  26. Vander Cruyssen B, Hoffman IE, Peene I, Union A, Mielants H, Meheus L, et al. Prediction models for rheumatoid arthritis during diagnostic investigation: evaluation of combinations of rheumatoid factor, anti-citrullinated protein/peptide antibodies and the human leucocyte antigen-shared epitope. Ann Rheum Dis. 2007;66:364–9.

    Article  CAS  PubMed  Google Scholar 

  27. Van Aken J, van Dongen H, le Cessie S, Allaart CF, Breedveld FC, Huizinga TW. Long-term outcome of rheumatoid arthritis that presented with undifferentiated arthritis compared to rheumatoid arthritis at presentation: an observational cohort study. Ann Rheum Dis. 2006;65:20–5.

    Article  PubMed  Google Scholar 

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Conflict of interest statement

All the authors responsible for this article declare that no conflict of interest of any kind exists.

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Authors and Affiliations

  1. Department of Rheumatology and Rehabilitation, Faculty of Medicine, Cairo University, Al-Saray Street, El Manial, Cairo, 11956, Egypt

    Yasser Emad

  2. Department of Rheumatology, Dr Erfan and Bagedo General Hospital, Jeddah, KSA

    Yasser Emad

  3. Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Al-Saray Street, El Manial, Cairo, 11956, Egypt

    Mohamed Shehata

  4. Department of Radiology, Faculty of Medicine, Cairo University, Al-Saray Street, El Manial, Cairo, 11956, Egypt

    Yasser Ragab

  5. Department of Radiology, Dr Erfan and Bagedo General Hospital, Jeddah, KSA

    Yasser Ragab & Hosny Hamza

  6. Department of Internal Medicine, Faculty of Medicine, Cairo University, Al-Saray Street, El Manial, Cairo, 11956, Egypt

    Ahmed Saad

  7. Department of Internal Medicine, Dr Erfan and Bagedo General Hospital, Jeddah, KSA

    Ahmed Saad

  8. Department of Radiology, Ain Shams University, Abbasyia, Cairo, 11556, Egypt

    Hosny Hamza

  9. Department of Public Health, Cairo University, Al-Saray Street, El Manial, Cairo, 11956, Egypt

    Alaa Abou-Zeid

Authors
  1. Yasser Emad
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  2. Mohamed Shehata
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  3. Yasser Ragab
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  4. Ahmed Saad
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  5. Hosny Hamza
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  6. Alaa Abou-Zeid
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Correspondence to Yasser Emad.

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Emad, Y., Shehata, M., Ragab, Y. et al. Prevalence and predictive value of anti-cyclic citrullinated protein antibodies for future development of rheumatoid arthritis in early undifferentiated arthritis. Mod Rheumatol 20, 358–365 (2010). https://doi.org/10.1007/s10165-010-0286-6

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  • DOI: https://doi.org/10.1007/s10165-010-0286-6

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