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Anti-cyclic citrullinated peptide-2 (CCP2) autoantibodies and extra-articular manifestations in Greek patients with rheumatoid arthritis

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Abstract

The objective of our study was to establish whether there is an association between rheumatoid arthritis with extra-articular manifestations (exRA) and anti-cyclic citrullinated peptide 2 (anti-CCP2) antibodies in Greeks. A retrospective study of 220 Greek patients with RA, 95 with exRA and 125 without extra-articular manifestations (cRA). Serum anti-CCP2 antibodies and IgM rheumatoid factor (RF) were measured. CCP2(+) were 65.3% of exRA and 58.4% of cRA patients. RF(+) were 69.5% of exRA and 60.0% of cRA patients. Among exRA patients, 37.9% had high serum anti-CCP2 antibody levels (>100 IU/ml) compared to 21.6% cRA patients (p = 0.008). Serositis and pulmonary fibrosis were found to be associated with high levels of anti-CCP2 antibodies (52.9 vs 26.6%, p = 0.02 and 63.6 vs 26.8%, p = 0.008, respectively). Serum RF levels were 265.0 ± 52.0 IU/ml (mean ± SEM) in exRA and 205.1 ± 40.6 (mean ± SEM) in cRA (NS). High serum RF levels (>268 IU/ml) were more likely to have sicca syndrome. In Greek patients with rheumatoid arthritis (RA), high serum anti-CCP2 antibodies are associated with serositis and pulmonary fibrosis. Therefore, anti-CCP2 antibodies have prognostic significance in patients with RA.

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References

  1. Gabriel SE, Crowson CS, Kremers HM et al (2003) Survival in rheumatoid arthritis. A population-based analysis of trends over 40 years. Arthritis Rheum 48:54–8

    Google Scholar 

  2. Ronnelid J, Wick MC, Lampa J et al (2005) Longitudinal analysis of citrullinated protein/peptide antibodies (anti-CCP) during 5 year follow up in early rheumatoid arthritis: anti-CCP status predicts worse disease activity and greater radiological progression. Ann Rheum Dis 64:1744–49

    Article  PubMed  CAS  Google Scholar 

  3. Turesson C, Jacobsson LTH, Sturfelt G et al (2007) Rheumatoid factor and antibodies to cyclic citrullinated peptides are associated with severe extra-articular manifestations in rheumatoid arthritis. Ann Rheum Dis 66:59–64

    Article  PubMed  CAS  Google Scholar 

  4. van Gaalen FA, van Aken J, Huizinga TWJ et al (2004) Association between HLA class II genes and autoantibodies to cyclic citrullinated peptides (CCPs) influence the severity of rheumatoid arthritis. Arthritis Rheum 50:2113–21

    Article  PubMed  CAS  Google Scholar 

  5. Van der Helm-van Mil AH, Verpoort KN, Breedveld FC et al (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 to develop rheumatoid arthritis. Arthritis Rheum 54:1117–21

    Article  PubMed  CAS  Google Scholar 

  6. Boki KA, Panayi GS, Vaughan RW et al (1992) HLA-class II sequence polymorphisms and susceptibility to rheumatoid arthritis in Greeks. The HLA-DR beta shared epitope accounts for the disease in only a minority of Greeks. Arthritis Rheum 35:749–55

    Article  PubMed  CAS  Google Scholar 

  7. Alexiou I, Germenis A, Ziogas A et al (2007) Diagnostic value of anti-cyclic citrullinated peptide antibodies in Greek patients with rheumatoid arthritis. BMC Musculoskelet Disord 8:37–43

    Article  PubMed  CAS  Google Scholar 

  8. Zendman AJW, van Venrooij WJ, Pruijn GJM (2006) Use and significance of anti-CCP autoantibodies in rheumatoid arthritis. Rheumatology 45:20–25

    Article  PubMed  CAS  Google Scholar 

  9. Nishimura K, Sugiyama D, Kogata Y et al (2007) Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody and rheumatoid a factor for rheumatoid arthritis. Ann Intern Med 146:816–7

    Google Scholar 

  10. De Rycke L, Peene I, Hoffman IEA et al (2004) Rheumatoid factor and anti-citrullinated protein antibodies in rheumatoid arthritis: diagnostic value, associations with radiological progression rate, and extra-articular manifestations. Ann Rheum Dis 63:1587–93

    Article  PubMed  CAS  Google Scholar 

  11. Korkmaz C, Us T, Kasifoglu T, Akgun Y (2006) Anti-cyclic citrullinated peptide (CCP) antibodies in patients with long-standing rheumatoid arthritis and their relationship with extra-articular manifestations. Clin Biochem 39:961–5

    Article  PubMed  CAS  Google Scholar 

  12. Klareskog L, Stolt P, Lundendberg K et al (2006) A new model for the etiology of rheumatoid arthritis: smoking may trigger HLA-DR (shared epitope)-restricted immune reaction to autoantigens modified by citrullination. Arthritis Rheum 54:38–46

    Article  PubMed  CAS  Google Scholar 

  13. Pedersen M, Jacobsen S, Garred P et al (2007) Strong combined gene-environment effects in anti-cyclic citrullinated peptide-positive rheumatoid arthritis. A nationwide case-control study in Denmark. Arthritis Rheum 56:1446–53

    Article  PubMed  Google Scholar 

  14. Stavropoulos C, Spyropoulou M, Koumantaki Y et al (1997) HLA-DRB1* genotypes in Greek rheumatoid arthritis patients: association with disease characteristics, sex and age at onset. Br J Rheumatol 36:141–2

    Article  PubMed  CAS  Google Scholar 

  15. Voskuyl AE, Zwinderman AH, Westedt ML et al (1996) Factors associated with the development of vasculitis in rheumatoid arthritis: results of a case-control study. Ann Rheum Dis 55:190–2

    Article  PubMed  CAS  Google Scholar 

  16. Alessandri C, Bombardieri M, Papa N et al (2004) Decrease of anti-cyclic citrullinated peptide antibodies and rheumatoid factor following anti-TNFα therapy (infliximab) in rheumatoid arthritis is associated with clinical improvement. Ann Rheum Dis 63:1218–21

    Article  PubMed  CAS  Google Scholar 

  17. Caramaschi P, Biasi D, Tonolli E et al (2005) Antibodies against cyclic citrullinated peptides in patients with rheumatoid arthritis before and after infliximab treatment. Rheumatol Int 26:58–62

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Lazaros I. Sakkas.

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Alexiou, I., Germenis, A., Koutroumpas, A. et al. Anti-cyclic citrullinated peptide-2 (CCP2) autoantibodies and extra-articular manifestations in Greek patients with rheumatoid arthritis. Clin Rheumatol 27, 511–513 (2008). https://doi.org/10.1007/s10067-007-0800-1

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  • DOI: https://doi.org/10.1007/s10067-007-0800-1

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