Publication
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
Journal Paper/Review - Feb 1, 2008
Schmechel Silke, Konrad Astrid, Diegelmann Julia, Glas Jürgen, Wetzke Martin, Paschos Ekaterini, Lohse Peter, Göke Burkhard, Brand Stephan
Units
PubMed
Doi
Citation
Type
Journal
Publication Date
Issn Print
Pages
Brief description/objective
BACKGROUND
We analyzed the influence of Crohn's disease (CD)-associated IL23R gene variants on IL-22 that is expressed in IL-23R+ 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-alpha, 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 = 2.53 x 10(-9)). IL-22 serum levels correlated with disease activity: IL-22 levels in patients with a Crohn's disease activity index (CDAI) >150 were significantly higher than in patients with a CDAI <150 (P = 0.001), while TNF-alpha 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 = 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 = 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-alpha. IL23R genotypes influence IL-22 serum expression, linking genetic CD susceptibility to Th17 cell function for the first time.