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

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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.

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Keywords

  • Rheumatoid Arthritis
  • Rheumatoid Arthritis Patient
  • Rheumatoid Factor
  • Joint Destruction
  • Autoantibody Production