title: 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.
abstract: 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.
authors.affiliation: Department of Medicine II, Grosshadern, University of Munich, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Schmechel
authors.forename: Astrid
authors.initials: A
authors.lastname: Konrad
authors.forename: Julia
authors.initials: J
authors.lastname: Diegelmann
authors.forename: Jürgen
authors.initials: J
authors.lastname: Glas
authors.forename: Martin
authors.initials: M
authors.lastname: Wetzke
authors.forename: Ekaterini
authors.initials: E
authors.lastname: Paschos
authors.forename: Peter
authors.initials: P
authors.lastname: Lohse
authors.forename: Burkhard
authors.initials: B
authors.lastname: Göke
authors.forename: Stephan
authors.initials: S
authors.lastname: Brand
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003424:Crohn Disease / Q000235:genetics* / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D005858:Germany; D006801:Humans; D007378:Interleukins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D018123:Receptors, Interleukin / Q000235:genetics* / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D044465:White People / Q000235:genetics; D000097043:Interleukin-22
chemical_list: D015415:Biomarkers; D007378:Interleukins; D053473:Nod2 Signaling Adaptor Protein; D018123:Receptors, Interleukin; D000097043:Interleukin-22; C515500:IL23R protein, human