Anti-cyclic citrullinated peptide antibody isotypes in rheumatoid arthritis: Association with disease duration, rheumatoid factor production and the presence of shared epitope

Gabriella Lakos, Lilla Soós, Andrea Fekete, Zoltaán Szabó, Margit Zeher, Ildikó F. Horváth, Katalin Dankó, Aniko Kapitány, Agnes Gyetvai, Gyula Szegedi, Zoltán Szekanecz

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Objective: Anti-cyclic citrullinated peptide (anti-CCP) antibodies of IgG isotype are specific diagnostic markers of rheumatoid arthritis (RA). Recent evidence also points to their direct involvement in the pathophysiology. Little information is available, however, regarding the isotype distribution of anti-CCP antibodies and the characteristics of IgA and IgM anti-CCP. Methods: IgG, IgA and IgM anti-CCP2 and rheumatoid factor (RF) levels were measured in the sera of 119 RA patients and 118 controls, including patients with other rheumatic diseases and healthy subjects. We analyzed the diagnostic performance of IgA and IgM anti-CCP2 antibodies and their relationship with IgG anti-CCP2, RFs, disease duration and the presence of HLA-DRB1 shared epitope (SE) alleles. Results: Patients with RA had significantly higher serum IgA and IgM anti-CCP2 antibody levels than healthy subjects and patients with other rheumatic diseases (p<0.0001). IgG, IgA and IgM anti-CCP2 antibodies were present in 74.8%, 52.9% and 44.5% of RA patients, and their diagnostic specificity was 95.8%, 95.8% and 91.6%, respectively. The presence of anti-CCP2 antibodies was significantly associated with SE alleles (p=0.03). The frequency of IgM anti-CCP2 positivity was lower in longstanding disease compared to early RA (p=0.03). Conclusion: IgA and IgM anti-CCP2 antibodies are present in RA patients, and they are similarly specific for RA as IgG anti-CCP2. The higher frequency of IgM anti-CCP2 antibodies in early RA suggests that they are mostly generated during the first phase of immune response; nonetheless, their production seems to be sustained in some patients. Further analysis of IgM and IgA anti-CCP2 antibodies may provide insights into the pathogenesis of RA.

Original languageEnglish
Pages (from-to)253-260
Number of pages8
JournalClinical and experimental rheumatology
Issue number2
Publication statusPublished - Mar 1 2008



  • Anti-CCP2
  • Duration of RA
  • IgA
  • IgM
  • Rheumatoid arthritis

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

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