Search in the Abstract Database

Search Abstracts 2011

* = Presenting author

P019. Expression of intestinal alpha-defensins in paediatric inflammatory bowel disease

M. Zilbauer1, A. Jenke2, A. Philips3, F. Torrente1, R. Heuschkel1, S. Wirth2

1Cambridge University, Department of Paediatric Gastroenterology, Cambridge, United Kingdom; 2HELIOS Klinikum, Department of Paediatrics, Wuppertal, Germany; 3Royal Free Hospital, Centre for Paediatric Gastroenterology, London, United Kingdom

Background: Reduced alpha-defensin expression has been reported in the terminal ileum (TI) of adult patients with ileal Crohn's disease (CD). However, it remains unclear whether this is causative or due to epithelial cell loss in long standing disease. Moreover, little is known about alpha-defensin expression in children with chronic inflammatory bowel disease.

Methods: 283 intestinal biopsies were obtained from children with CD, ulcerative colitis (UC) and healthy controls. Absolute mRNA copy numbers for HD5, HD6, IL-8, Villin 1 and Tcf-4 were analyzed by RT-PCR. HD5 immunostaining was performed on biopsy sections and patients genotyped for NOD2 mutations.

Results: Equal expression levels of HD5 and HD6 were found in TI biopsies of children with ileal CD (L1+L3) compared to patients with isolated colonic disease (L2) and healthy controls. In contrast, we found significantly higher levels of alpha-defensins in the TI of children with UC. Reduced expression of Tcf-4 was observed in the duodenum and TI of CD patients with L1+L3 phenotype. We demonstrate significant up-regulation of HD5 and HD6 by metaplastic Paneth cells in the inflamed colon of children with IBD.

Conclusions: In this study no difference in alpha-defensin expression was found in the TI of CD children and controls. However, significant reduction of Tcf-4 in L1+L3 phenotype suggests that impaired PC differentiation may lead to altered HD5 and HD6 expression at a later stage of disease. Additionally, substantial up-regulation of alpha-defensins in the inflamed colonic mucosa raises the question for their potential involvement in modulating inflammation in paediatric colonic IBD.