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Clin Immunol. 2018 May;190:15-21. doi: 10.1016/j.clim.2018.02.010. Epub 2018 Feb 24.

IL10 promoter haplotypes may contribute to altered cytokine expression and systemic inflammation in celiac disease.

Author information

1
Department of Pediatrics, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
2
Institute of Translational Immunology, University Medical Center, Johannes Gutenberg University, Mainz, Germany; Research Center for Immunotherapy, University Medical Center, Johannes Gutenberg University, Mainz, Germany; Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
3
Institute of Translational Immunology, University Medical Center, Johannes Gutenberg University, Mainz, Germany; Research Center for Immunotherapy, University Medical Center, Johannes Gutenberg University, Mainz, Germany.
4
Department of Pediatrics, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Department of Women's & Children's Health, Institute of Translational Medicine, University of Liverpool, Liverpool, UK; Department of Paediatric Rheumatology, Alder Hey Children's NHS Foundation Trust Hospital, Liverpool, UK. Electronic address: Christian.hedrich@liverpool.ac.uk.

Abstract

Celiac disease (CD) is an autoimmune/inflammatory condition triggered by dietary gluten intake in genetically predisposed individuals. Though associations with MHC class II HLA-DQ2 or -DQ8 are the primary and necessary genetic predisposition for CD, >97% of genetically predisposed individuals never develop CD. Cytokines were measured in the serum of CD patients and controls. Possible associations with IL10 promoter variants were investigated. Cytokine expression from PBMCs was monitored in response to gluten exposure, or CD3/TCR complex stimulation in the absence or presence of recombinant IL-10. Serum cytokines varied between patients with CD at the time of diagnosis, after dietary elimination of gluten, and healthy controls. Serum IL-17A reflected disease activity. Reduced IL-10 serum levels and altered IL-10 expression by PBMCs coincided with IL10 promoter haplotypes that encode for "low" IL-10 expression (ATA). Increased prevalence of ATA IL10 promoter haplotypes and subsequently reduced IL-10 expression may be an immunological cofactor in individuals genetically predisposed for the development of CD. Resulting cytokine imbalances may be utilized as disease biomarkers in CD.

PMID:
29481982
DOI:
10.1016/j.clim.2018.02.010
[Indexed for MEDLINE]

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