Analysis of IL17A and IL21 Expression in the Small Intestine of Celiac Disease Patients and Correlation with Circulating Thioredoxin Level

Genet Test Mol Biomarkers. 2018 Sep;22(9):518-525. doi: 10.1089/gtmb.2018.0128. Epub 2018 Sep 5.

Abstract

Aims: Th17 cells and their related cytokines play an important role in the pathogenesis of celiac disease (CD), and thioredoxin (Trx) is an extracellular TG2 activity regulator. This study evaluated Trx serum levels and the expression levels of IL17A, IL21, and Trx genes in biopsies of treated (gluten-free diet) and naïve (untreated) CD patients compared with healthy individuals.

Methods: Duodenal biopsies were collected from treated CD patients (n = 60), healthy controls (n = 60), and eight newly diagnosed celiac patients. IL17A, IL21, and Trx gene expression was assessed by quantitative polymerase chain reaction (qPCR) and compared with serum Trx levels assessed by enzyme-linked immunosorbent assay (ELISA).

Results: Expression levels of the IL21 and Trx genes were not significantly modulated in the CD group compared to the control group, whereas the IL17A gene in CD patients was transcribed at significantly higher levels among the CD group. Serum concentrations of Trx were significantly increased in treated CD patients compared to the control group.

Conclusions: We observed that IL17A gene is more highly expressed in duodenal biopsies of CD patients than controls, and that the serum levels of Trx are significantly higher in treated CD patients than controls. Therefore, the expression levels of these genes and gene products, respectively, could potentially be used as diagnostic biomarkers for CD patients, although more studies are needed to unravel the underlying molecular mechanisms.

Keywords: IL17A; IL21; celiac disease; gene expression; thioredoxin.

MeSH terms

  • Adult
  • Biopsy
  • Celiac Disease / blood
  • Celiac Disease / genetics*
  • Celiac Disease / metabolism
  • Celiac Disease / pathology
  • Female
  • Humans
  • Interleukin-17 / biosynthesis*
  • Interleukin-17 / genetics
  • Interleukins / biosynthesis*
  • Interleukins / genetics
  • Intestine, Small / metabolism
  • Intestine, Small / pathology
  • Male
  • Th17 Cells / metabolism
  • Th17 Cells / pathology
  • Thioredoxins / blood*
  • Transcriptome

Substances

  • IL17A protein, human
  • Interleukin-17
  • Interleukins
  • Thioredoxins
  • interleukin-21