Role of proneurotensin as marker of paediatric coeliac disease

Research output: Contribution to journalArticle

Abstract

Neurotensin (NT) is a gut hormone functioning proinflammatory through nuclear factor kappa B (NF-κB) and interleukin (IL)−8 secretion or anti-inflammatory through epidermal growth factor receptors. NT mRNA is down-regulated in duodenal biopsies of children with untreated coeliac disease. The aim of this study was to investigate if plasma pro-NT levels correlated with the degree of intestinal mucosal damage and tissue transglutaminase autoantibody (tTGA) levels in children with coeliac disease. Fasting plasma samples from 96 children with coeliac disease and 89 non-coeliac disease controls were analysed for NT precursor fragment pro-NT 1–117 by a chemiluminometric immunoassay. Pro-NT levels were compared with NT mRNA from duodenal biopsies, assessed previously with quantitative polymerase chain reaction (PCR). Illumina core exome arrays were used for human leucocyte antigen (HLA) typing and the Marsh criteria applied to score mucosal damage. Tissue TGA was measured by radio binding assay. A general linear model compared pro-NT levels with diagnosis of coeliac disease, Marsh score and HLA DQ haplotype. Spearman's rank test was used to compare pro-NT levels with tTGA, age and duodenal NT mRNA levels, respectively. Plasma pro-NT levels were elevated in children with coeliac disease (median 23 pmol/l higher, P = 0·003) and in those with severe intestinal mucosal damage (median 24 pmol/l higher for ≥ Marsh 3b versus not, P = 0·0004). Pro-NT levels correlated further with tTGA (r2 = 0·22, P = 0·002), but not with duodenal NTS mRNA levels (r2 = −0·12, P = 0·14). Pro-NT was not associated with any of the HLA risk-haplotypes. Elevated peripheral pro-NT levels reflect more severe forms of active coeliac disease, indicating a potential role of NT in intestinal inflammation.

Details

Authors
Organisations
External organisations
  • University of Gothenburg
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area
  • Endocrinology and Diabetes

Keywords

  • children, coeliac disease, inflammation, neurotensin
Original languageEnglish
Pages (from-to)387-392
Number of pages6
JournalClinical and Experimental Immunology
Volume186
Issue number3
Publication statusPublished - 2016 Dec 1
Publication categoryResearch
Peer-reviewedYes