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Diagnostic utility of anti-cyclic citrullinated peptide antibodies for rheumatoid arthritis in patients with active lung tuberculosis

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Abstract

This study was intended to evaluate the utility of anti-cyclic citrullinated peptide antibodies (second generation, anti-CCP2) as a diagnostic marker for rheumatoid arthritis (RA) in patients with active tuberculosis. Among 89 patients with active tuberculosis, anti-CCP2 was detected in six (6.7%), and three of these (3.4%) were strongly positive for anti-CCP2. The positive rate of anti-CCP2 in patients with newly diagnosed RA was 82.1% (87 of 106 cases), while the rate in healthy control subjects was 0.4% (one of 237 individuals). The mean level of anti-CCP2 among the RA group was 159.3 U/ml, which was significantly higher than both that among the tuberculosis group (15.4 U/ml) and that among the healthy controls (0.7 U/ml). IgM rheumatoid factor (RF) was detected in 16 patients from the tuberculosis group (18.0%) with a mean serum level of 18.6 IU/ml and in 77 patients of the RA group (72.6%) with a mean level of 164.0 IU/ml. Only two cases in the tuberculosis group were positive for both anti-CCP2 and IgM RF. These observations show that measurement of anti-CCP2 seems to be a reliable serological tool for identifying early RA in patients with active tuberculosis.

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References

  1. Schellekens GA, Visser H, de Jong BA et al (2000) The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide. Arthritis Rheum 43:155–163

    Article  PubMed  CAS  Google Scholar 

  2. Kroot EJ, de Jong BA, van Leeuwen MA et al (2000) The prognostic value of anti-cyclic citrullinated peptide antibody in patients with recent-onset rheumatoid arthritis. Arthritis Rheum 43:1831–1835

    Article  PubMed  CAS  Google Scholar 

  3. van Gaalen FA, Visser H, Huizinga TW (2005) A comparison of the diagnostic accuracy and prognostic value of the first and second anti-cyclic citrullinated peptides (CCP1 and CCP2) autoantibody tests for rheumatoid arthritis. Ann Rheum Dis 64:1510–1512

    Article  PubMed  Google Scholar 

  4. Lee DM, Schur PH (2003) Clinical utility of the anti-CCP assay in patients with rheumatic diseases. Ann Rheum Dis 62:870–874

    Article  PubMed  CAS  Google Scholar 

  5. Syversen SW, Gaarder PI, Goll GL et al (2008) High anti-cyclic citrullinated peptide levels and an algorithm of four variables predict radiographic progression in patients with rheumatoid arthritis: results from a 10-year longitudinal study. Ann Rheum Dis 67:212–217

    Article  PubMed  CAS  Google Scholar 

  6. Avouac J, Gossec L, Dougados M (2006) Diagnostic and predictive value of anti-cyclic citrullinated protein antibodies in rheumatoid arthritis: a systematic literature review. Ann Rheum Dis 65:845–851

    Article  PubMed  CAS  Google Scholar 

  7. van Gaalen FA, Linn-Rasker SP, van Venrooij WJ et al (2004) Autoantibodies to cyclic citrullinated peptides predict progression to rheumatoid arthritis in patients with undifferentiated arthritis: a prospective cohort study. Arthritis Rheum 50:709–715

    Article  PubMed  Google Scholar 

  8. Rantapaa-Dahlqvist S, de Jong BA, Berglin E et al (2003) Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Arthritis Rheum 48:2741–2749

    Article  PubMed  Google Scholar 

  9. Berglin E, Johansson T, Sundin U et al (2006) Radiological outcome in rheumatoid arthritis is predicted by presence of antibodies against cyclic citrullinated peptide before and at disease onset, and by IgA-RF at disease onset. Ann Rheum Dis 65:453–458

    Article  PubMed  CAS  Google Scholar 

  10. Visser H, le Cessie S, Vos K, Breedveld FC, Hazes JM (2002) How to diagnose rheumatoid arthritis early: a prediction model for persistent (erosive) arthritis. Arthritis Rheum 46:357–365

    Article  PubMed  Google Scholar 

  11. Sene D, Ghillani-Dalbin P, Limal N et al (2006) Anti-cyclic citrullinated peptide antibodies in hepatitis C virus associated rheumatological manifestations and Sjogren’s syndrome. Ann Rheum Dis 65:394–397

    Article  PubMed  CAS  Google Scholar 

  12. Mediwake R, Isenberg DA, Schellekens GA, van Venrooij WJ (2001) 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 60:67–68

    Article  PubMed  CAS  Google Scholar 

  13. Wener MH, Hutchinson K, Morishima C, Gretch DR (2004) Absence of antibodies to cyclic citrullinated peptide in sera of patients with hepatitis C virus infection and cryoglobulinemia. Arthritis Rheum 50:2305–2308

    Article  PubMed  CAS  Google Scholar 

  14. Bombardieri M, Alessandri C, Labbadia G et al (2004) Role of anti-cyclic citrullinated peptide antibodies in discriminating patients with rheumatoid arthritis from patients with chronic hepatitis C infection-associated polyarticular involvement. Arthritis Res Ther 6:R137–R141

    Article  PubMed  CAS  Google Scholar 

  15. Gottenberg JE, Mignot S, Nicaise-Rolland P et al (2005) Prevalence of anti-cyclic citrullinated peptide and anti-keratin antibodies in patients with primary Sjogren’s syndrome. Ann Rheum Dis 64:114–117

    Article  PubMed  CAS  Google Scholar 

  16. Elkayam O, Segal R, Lidgi M, Caspi D (2006) Positive anti-cyclic citrullinated proteins and rheumatoid factor during active lung tuberculosis. Ann Rheum Dis 65:1110–1112

    Article  PubMed  CAS  Google Scholar 

  17. van Venrooij WJ, Hazes JM, Visser H (2002) Anticitrullinated protein/peptide antibody and its role in the diagnosis and prognosis of early rheumatoid arthritis. Neth J Med 60:383–388

    PubMed  Google Scholar 

  18. Matsui T, Shimada K, Ozawa N et al (2006) Diagnostic utility of anti-cyclic citrullinated peptide antibodies for very early rheumatoid arthritis. J Rheumatol 33:2390–2397

    PubMed  CAS  Google Scholar 

  19. van der Helm-van Mil AH, Verpoort KN, Breedveld FC, Huizinga TW, Toes RE, de Vries RR (2006) The HLA-DRB1 shared epitope alleles are primarily a risk factor for anti-cyclic citrullinated peptide antibodies and are not an independent risk factor for development of rheumatoid arthritis. Arthritis Rheum 54:1117–1121

    Article  PubMed  Google Scholar 

  20. Irigoyen P, Lee AT, Wener MH et al (2005) Regulation of anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis: contrasting effects of HLA-DR3 and the shared epitope alleles. Arthritis Rheum 52:3813–3818

    Article  PubMed  CAS  Google Scholar 

  21. Huizinga TW, Amos CI, van der Helm-van Mil AH et al (2005) Refining the complex rheumatoid arthritis phenotype based on specificity of the HLA-DRB1 shared epitope for antibodies to citrullinated proteins. Arthritis Rheum 52:3433–3438

    Article  PubMed  CAS  Google Scholar 

  22. Suzuki A, Yamada R, Chang X et al (2003) Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis. Nat Genet 34:395–402

    Article  PubMed  CAS  Google Scholar 

  23. Cha S, Choi CB, Han TU, Kang CP, Kang C, Bae SC (2007) Association of anti-cyclic citrullinated peptide antibody levels with PADI4 haplotypes in early rheumatoid arthritis and with shared epitope alleles in very late rheumatoid arthritis. Arthritis Rheum 56:1454–1463

    Article  PubMed  CAS  Google Scholar 

  24. Caponi L, Petit-Teixeira E, Sebbag M et al (2005) A family based study shows no association between rheumatoid arthritis and the PADI4 gene in a white French population. Ann Rheum Dis 64:587–593

    Article  PubMed  CAS  Google Scholar 

  25. Hoppe B, Haupl T, Gruber R et al (2006) Detailed analysis of the variability of peptidylarginine deiminase type 4 in German patients with rheumatoid arthritis: a case-control study. Arthritis Res Ther 8:R34

    Article  PubMed  Google Scholar 

  26. Barton A, Bowes J, Eyre S et al (2004) A functional haplotype of the PADI4 gene associated with rheumatoid arthritis in a Japanese population is not associated in a United Kingdom population. Arthritis Rheum 50:1117–1121

    Article  PubMed  CAS  Google Scholar 

  27. Dubucquoi S, Solau-Gervais E, Lefranc D et al (2004) Evaluation of anti-citrullinated filaggrin antibodies as hallmarks for the diagnosis of rheumatic diseases. Ann Rheum Dis 63:415–419

    Article  PubMed  CAS  Google Scholar 

  28. Fernandez-Suarez A, Reneses S, Wichmann I, Criado R, Nunez A (2005) Efficacy of three ELISA measurements of anti-cyclic citrullinated peptide antibodies in the early diagnosis of rheumatoid arthritis. Clin Chem Lab Med 43:1234–1239

    Article  PubMed  CAS  Google Scholar 

  29. Greiner A, Plischke H, Kellner H, Gruber R (2005) Association of anti-cyclic citrullinated peptide antibodies, anti-citrullin antibodies, and IgM and IgA rheumatoid factors with serological parameters of disease activity in rheumatoid arthritis. Ann N Y Acad Sci 1050:295–303

    Article  PubMed  CAS  Google Scholar 

  30. Garcia-Berrocal B, Gonzalez C, Perez M et al (2005) Anti-cyclic citrullinated peptide autoantibodies in IgM rheumatoid factor-positive patients. Clin Chim Acta 354:123–130

    Article  PubMed  CAS  Google Scholar 

  31. Suzuki K, Sawada T, Murakami A et al (2003) High diagnostic performance of ELISA detection of antibodies to citrullinated antigens in rheumatoid arthritis. Scand J Rheumatol 32:197–204

    Article  PubMed  CAS  Google Scholar 

  32. Malaviya AN, Kotwal PP (2003) Arthritis associated with tuberculosis. Best Pract Res Clin Rheumatol 17:319–343

    Article  PubMed  CAS  Google Scholar 

  33. Yamada T, Nakajima A, Inoue E et al (2006) Increased risk of tuberculosis in patients with rheumatoid arthritis in Japan. Ann Rheum Dis 65:1661–1663

    Article  PubMed  CAS  Google Scholar 

  34. Carmona L, Hernandez-Garcia C, Vadillo C et al (2003) Increased risk of tuberculosis in patients with rheumatoid arthritis. J Rheumatol 30:1436–1439

    PubMed  Google Scholar 

  35. Guedes-Barbosa LS, Mangueira C, Scheinberg M (2008) Anticitrulline peptide antibodies (CCP3) in leprosy sera: a negative association. Clin Rheumatol 27:515–516

    Article  PubMed  Google Scholar 

  36. Makrygiannakis D, af Klint E, Lundberg IE et al (2006) Citrullination is an inflammation-dependent process. Ann Rheum Dis 65:1219–1222

    Article  PubMed  CAS  Google Scholar 

  37. Vossenaar ER, Nijenhuis S, Helsen MM et al (2003) Citrullination of synovial proteins in murine models of rheumatoid arthritis. Arthritis Rheum 48:2489–2500

    Article  PubMed  CAS  Google Scholar 

  38. Vossenaar ER, Smeets TJ, Kraan MC, Raats JM, van Venrooij WJ, Tak PP (2004) The presence of citrullinated proteins is not specific for rheumatoid synovial tissue. Arthritis Rheum 50:3485–3494

    Article  PubMed  CAS  Google Scholar 

  39. Kakumanu P, Yamagata H, Sobel ES, Reeves WH, Chan EK, Satoh M (2008) Patients with pulmonary tuberculosis are frequently positive for anti-cyclic citrullinated peptide antibodies, but their sera also react with unmodified arginine-containing peptide. Arthritis Rheum 58:1576–1581

    Article  PubMed  CAS  Google Scholar 

  40. Vannini A, Cheung K, Fusconi M et al (2007) Anti-cyclic citrullinated peptide positivity in non-rheumatoid arthritis disease samples: citrulline-dependent or not? Ann Rheum Dis 66:511–516

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Clinical Research Center for Rheumatic Disease and Department of Rheumatology, Kumamoto Saishunsou National Hospital, 2659 Suya, Kohshi, Kumamoto, 861-1196, Japan

    Shunsuke Mori

  2. Department of Medicine, Kumamoto Kohnan Hospital, Kumamoto, Japan

    Hiromichi Naito

  3. Department of Medicine, Minami Yokohama National Hospital, Yokohama, Japan

    Sumire Ohtani

  4. Department of Medicine, Kumamoto Minami National Hospital, Kumamoto, Japan

    Tohru Yamanaka

  5. Division of Respiratory Medicine, Department of Medicine, Kumamoto Saishunsou National Hospital, Kumamoto, Japan

    Mineharu Sugimoto

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  1. Shunsuke Mori
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  2. Hiromichi Naito
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  3. Sumire Ohtani
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  4. Tohru Yamanaka
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  5. Mineharu Sugimoto
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Correspondence to Shunsuke Mori.

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Mori, S., Naito, H., Ohtani, S. et al. Diagnostic utility of anti-cyclic citrullinated peptide antibodies for rheumatoid arthritis in patients with active lung tuberculosis. Clin Rheumatol 28, 277–283 (2009). https://doi.org/10.1007/s10067-008-1035-5

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  • DOI: https://doi.org/10.1007/s10067-008-1035-5

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