Volume 5 Supplement 1

23rd European Workshop for Rheumatology Research

Open Access

A polymorphism in the IL-10 promoter affects autoantibody production and subsequent joint destruction in rheumatoid arthritis

  • FA van Gaalen1,
  • L Lard1,
  • J Schonkeren1,
  • E Pieterman1,
  • G Stoeken1,
  • K Vos1,
  • R Nelissen1,
  • R Westendorp1,
  • R Hoeben1,
  • FC Breedveld1,
  • R Toes1 and
  • TWJ Huizinga1
Arthritis Res Ther20035(Suppl 1):62

DOI: 10.1186/ar692

Received: 14 January 2003

Published: 24 February 2003

Background

Rheumatoid arthritis (RA) is a multifactorial, polygenic disease, in which the relevant pathways involved in its various stages are poorly understood. Interleukin-10 (IL-10) is known for its wide range of both anti-inflammatory and inflammatory effects on various cell types involved in RA.

Objective

To gain a better understanding of the role of IL-10 in RA, we analyzed in a prospective cohort of RA patients (n = 283) the -2849 A/G IL-10 promoter polymorphism, as this polymorphism is highly associated with high (AG/GG variants) or low (AA variant) IL-10 production.

Results

In our cohort, the IL-10 genotype was, in comparison with controls, not a risk factor for RA. But, RA patients with the -2849 genotypes associated with high IL-10 production, had, at baseline, significantly higher titers of IgG autoantibody (anti-CCP and IgG rheumatoid factor), but not of IgM autoantibody (IgM rheumatoid factor). Moreover, a higher rate of joint destruction was observed in RA with genotypes associated with high IL-10 production. However, invasiveness of fibroblast-like synoviocytes, which are thought to be important effectors of joint destruction, was not correlated with IL-10 genotypes.

Conclusion

The -2849 IL-10 promoter polymorphims associated with high IL-10 production were found in RA patients with high IgG autoantibody titers and an increased rate of joint destruction. As IL-10 is crucially involved in class-switching and function of B-cells, we propose that genetically determined differences in IL-10 production mediate their effect on joint destruction via increased autoantibody production by B cells.

Authors’ Affiliations

(1)
Department of Rheumatology, Leiden University Medical Center

Copyright

© BioMed Central Ltd 2003

Advertisement