Article

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.

Department of Medicine II, Grosshadern, University of Munich, Germany.
Inflammatory Bowel Diseases (Impact Factor: 5.12). 02/2008; 14(2):204-12. DOI: 10.1002/ibd.20315
Source: PubMed

ABSTRACT We analyzed the influence of Crohn's disease (CD)-associated IL23R gene variants on IL-22 that is expressed in IL-23R+ Th17 cells.
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.
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).
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.

0 Bookmarks
 · 
53 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The Guillain-Barré syndrome (GBS) is considered a T helper 1 (Th1) cells-mediated acute inflammatory peripheral neuropathy. However, some changes in GBS could not be explained completely by Th1 cells pathogenic role. Recently, Th17 cells have been identified and can mediate tissue inflammation and autoimmune response. Therefore, a study on the role of Th17 and Th22 cells and their cytokines in GBS is necessary for exploring the pathogenesis of GBS. Here, we detected the frequency of Th1, Th17, and Th22 cells by using 4-color flow cytometry and we detected the plasma levels of IL-17 and IL-22 by ELISA in GBS patients, relapsing-remitting multiple sclerosis patients at the acute phase of relapse, viral encephalitis or meningitis patients and healthy controls. Our data showed that the frequency of circulating Th1, Th17, and Th22 cells was significantly increased in GBS patients. The plasma levels of IL-17 and IL-22 in GBS and relapsing-remitting multiple sclerosis at the acute phase of relapse were also markedly elevated. Enhanced circulating Th22 cells were correlated with GBS severity. Intravenous immunoglobulin therapy downregulated Th17, and Th22 cells and the plasma levels of IL-17 and IL-22 in GBS patients. Th17 and Th22 cells may be involved in the pathogenesis of GBS, and intravenous immunoglobulin mediates therapeutic effects by downregulating these cells and their cytokines.
    Mediators of Inflammation 01/2014; 2014:740947. · 3.88 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Large granular lymphocytic (LGL) leukemia is an incurable chronic disease, characterized by clonal expansion of cytotoxic T- or NK-cells in blood and bone marrow. Cytopenias (anemia, neutropenia) and autoimmune disorders such as rheumatoid arthritis are the most common clinical manifestations of LGL leukemia. Recently, somatic activating STAT3 gene mutations were shown to be specific for LGL leukemia with a prevalence of up to 70%. Analogous mutations in the STAT5b gene were seen in a smaller proportion of patients. These gain-of-function mutations are located in the SH2 domain of STAT3 and affect the phosphotyrosine-SH2 interaction required for dimerization of STAT3. The mutations increase the phosphorylation of STAT3 and STAT5b and enhance the transcriptional activity of the mutated proteins. STAT3 and STAT5b mutations can be used as molecular markers for LGL leukemia diagnostics, and they present novel therapeutic targets for STAT3 and STAT5b inhibitors, which currently are in development for treatment of cancer and autoimmune disorders.
    Annals of medicine 02/2014; · 3.52 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Inflammatory bowel diseases (IBD) are chronic diseases of the gastrointestinal tract. Although their pathogenesis is unclear, the combination of genetic predisposition and environmental components are believed to be the main cause of these diseases. Recently, many variants in interleukin 23 receptor (IL23R) and autophagy-related 16-like 1 (ATG16L1) genes have been associated with the disease. Our objective was to assess the frequency of ATG16L1 (T300A) and IL23R (L310P) variants in Moroccan IBD (Crohn's disease and Ulcerative Colitis) patients and to evaluate a possible effect of these variants on disease's phenotype and clinical course.
    BMC Research Notes 08/2014; 7(1):570.

Full-text

View
0 Downloads