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Volume 9 Supplement 3

6th Global Arthritis Research Network (GARN) Meeting

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

Arthritis Research & Therapy volume 9, Article number: P16 (2007) Cite this article

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.

Author information

Affiliations

  1. Department of Rheumatology, Leiden University Medical Center, The Netherlands

    KN Verpoort, A Ioan-Facsinay, AHM van der Helm-van Mil, FC Breedveld, TWJ Huizinga & REM Toes

  2. Department of Biomolecular Chemistry, Radboud University Nijmegen, The Netherlands

    K Cheung & GJM Pruijn

  3. Department of Immunohaematology & Blood Transfusion, Leiden University Medical Center, The Netherlands

    RRP de Vries

Authors
  1. KN Verpoort
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  2. K Cheung
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  3. A Ioan-Facsinay
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  4. AHM van der Helm-van Mil
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  5. RRP de Vries
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  6. FC Breedveld
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  7. TWJ Huizinga
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  8. GJM Pruijn
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  9. REM Toes
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Verpoort, K., Cheung, K., Ioan-Facsinay, A. et al. Fine-specificity of the antibodies against citrullinated protein response is influenced by shared epitope alleles. Arthritis Res Ther 9, P16 (2007). https://doi.org/10.1186/ar2242

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Keywords

  • Rheumatoid Arthritis
  • Rheumatoid Arthritis Patient
  • Fibrinogen
  • Antibody Production
  • Citrullinated

Arthritis Research & Therapy

ISSN: 1478-6362

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