Linking genetic susceptibility to Crohn's disease with Th17 cell function: IL-22 serum levels are increased in Crohn's disease and correlate with disease activity and IL23R genotype status
✍ Scribed by Silke Schmechel; Astrid Konrad; Julia Diegelmann; Jürgen Glas; Martin Wetzke; Ekaterini Paschos; Peter Lohse; Burkhard Göke; Stephan Brand
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- English
- Weight
- 222 KB
- Volume
- 14
- Category
- Article
- ISSN
- 1078-0998
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✦ Synopsis
Background:
We analyzed the influence of Crohn's disease (CD)associated IL23R gene variants on IL-22 that is expressed in IL-23Rϩ Th17 cells.
Methods: IL-22 serum levels were measured in 242 CD patients and in 31 healthy controls. Subanalyses included serum levels of IL-6, TNF-␣, IL-17A, IL-17F, C-reactive protein (CRP), and leukocyte count. In all patients, genotyping for 10 CD-associated IL23R single nucleotide polymorphisms (SNPs) and the 3 main CD-associated CARD15 variants was performed.
Results: There was a highly significant increase in IL-22 serum expression in CD patients compared to healthy controls (P ϭ 2.53 ϫ 10 Ϫ9 ). IL-22 serum levels correlated with disease activity: IL-22 levels in patients with a Crohn's disease activity index (CDAI) Ͼ150 were significantly higher than in patients with a CDAI Ͻ150 (P ϭ 0.001), while TNF-␣ and IL-6 were not significantly different between these 2 groups. Analyzing the effect of 10 IL23R variants on IL-22 serum levels, we demonstrated that the quotients of mean IL-22 serum levels of carriers of the minor allele to the mean serum IL-22 in wildtype carriers correlated highly with the corresponding CD susceptibility risk for each gene variant (r ϭ 0.807). The IL-22 levels in carriers of CD risk-increasing IL23R variants were significantly higher than in carriers of CD risk-decreasing IL23R variants (P ϭ 0.008).
Conclusions:
The Th17 cytokine IL-22 is expressed at high levels in CD and correlates with disease activity, offering a better separation between active and inactive CD than IL-6 and TNF-␣. IL23R genotypes influence IL-22 serum expression, linking genetic CD susceptibility to Th17 cell function for the first time.