Advertisement

Fine-specificity of the antibodies against citrullinated protein response is influenced by shared epitope alleles

  • KN Verpoort
  • K Cheung
  • A Ioan-Facsinay
  • AHM van der Helm-van Mil
  • RRP de Vries
  • FC Breedveld
  • TWJ Huizinga
  • GJM Pruijn
  • REM Toes
Poster presentation

Keywords

Rheumatoid Arthritis Rheumatoid Arthritis Patient Fibrinogen Antibody Production Citrullinated 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Objective

In classic studies on the genetic background of antibody production, MHC has been shown to act as the most prominent immune-response gene that controls the magnitude and the specificity of antibody production. The strongest genetic risk factor for rheumatoid arthritis (RA), the human MHC, HLA-DRB1 shared epitope (SE) alleles, predisposes for antibodies against citrullinated proteins (ACPA). ACPA levels are higher in SE-positive than in SE-negative RA patients. The present study determines whether SE not only influences the magnitude, but also the specificity of the ACPA response.

Methods

In two independent cohorts of anti-CCP2-positive RA patients (n = 206 and n = 214 patients, respectively), serum antibodies against a citrullinated peptide derived from vimentin (cVim) and antibodies against a citrullinated fibrinogen peptide (cFibr) were determined by ELISA. HLA-DRB1 genotyping was performed.

Results

In the first cohort, SE alleles were significantly associated with the presence of antibodies against cVim (OR = 4.55, 95% CI = 1.78–12.9) and not significantly with the presence of antibodies against cFibr (OR = 1.81, 95% CI = 0.78–4.13). These results were replicated in the second cohort (OR = 4.13, 95% CI = 1.68–10.3 and OR = 1.08, 95% CI = 0.34–3.23, respectively).

Conclusion

In two cohorts of ACPA-positive RA patients, SE alleles predispose for the development of antibodies against cVim, and not for the development of antibodies against cFibr. These data indicate that SE alleles act as 'classic' immune-response genes in the ACPA response, as they influence both the magnitude and the specificity of this RA-specific antibody response.

Copyright information

© BioMed Central Ltd 2007

Authors and Affiliations

  • KN Verpoort
    • 1
  • K Cheung
    • 2
  • A Ioan-Facsinay
    • 1
  • AHM van der Helm-van Mil
    • 1
  • RRP de Vries
    • 3
  • FC Breedveld
    • 1
  • TWJ Huizinga
    • 1
  • GJM Pruijn
    • 2
  • REM Toes
    • 1
  1. 1.Department of RheumatologyLeiden University Medical CenterThe Netherlands
  2. 2.Department of Biomolecular ChemistryRadboud University NijmegenThe Netherlands
  3. 3.Department of Immunohaematology & Blood TransfusionLeiden University Medical CenterThe Netherlands

Personalised recommendations