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Intestinal alpha-defensin expression in pediatric inflammatory bowel disease
M Zilbauer1, A Jenke, G Wenzel
1Department of Paediatrics, HELIOS Klinikum Wuppertal, Germany. mz304@medschl.cam.ac.uk
Insights
Alpha-defensin expression in the ileum of pediatric Crohn's disease (CD) patients did not differ from controls. However, increased alpha-defensins were found in the inflamed colon of pediatric inflammatory bowel disease (IBD) patients.
Area of Science:
- Gastroenterology
- Immunology
- Pediatric Inflammatory Bowel Disease Research
Background:
- Alpha-defensin expression is reduced in adult Crohn's disease (CD) ileum.
- Limited data exists on alpha-defensin expression in pediatric inflammatory bowel disease (IBD).
Purpose of the Study:
- To investigate alpha-defensin (HD5, HD6) expression in pediatric CD and ulcerative colitis (UC).
- To assess the relationship between alpha-defensins, Tcf-4, and Paneth cell differentiation in pediatric IBD.
Main Methods:
- Analyzed 283 intestinal biopsies from pediatric CD, UC, and healthy controls using RT-PCR.
- Quantified mRNA copy numbers for HD5, HD6, IL-8, Villin 1, and Tcf-4.
- Performed HD5 immunostaining and NOD2 genotyping.
Main Results:
- Ileal alpha-defensin levels were similar in pediatric CD, UC, and controls.
- Significantly higher ileal alpha-defensins were observed in pediatric UC compared to CD and controls.
- Reduced Tcf-4 expression was found in the duodenum and ileum of pediatric CD patients with L1+L3 phenotype.
- Increased HD5 and HD6 expression occurred in the inflamed colon of pediatric IBD patients, linked to metaplastic Paneth cells.
Conclusions:
- No difference in ileal alpha-defensin expression between pediatric CD and controls.
- Reduced Tcf-4 in pediatric CD suggests potential impaired Paneth cell differentiation affecting alpha-defensin expression.
- Elevated alpha-defensin expression in inflamed pediatric IBD colons suggests a role in modulating inflammation.
Background:
Reduced alpha-defensin expression has been reported in the terminal ileum (TI) of adult patients with ileal Crohn's disease (CD). However, little is known about alpha-defensin expression in children with chronic inflammatory bowel disease (IBD).
Methods:
In all, 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 reverse-transcription polymerase chain reaction (RT-PCR). HD5 immunostaining was performed on biopsy sections and patients genotyped for NOD2 mutations.
Results:
Equal expression levels of alpha-defensins (HD5 and HD6) were found in TI biopsies of children with ileal CD (L1+L3) compared to patients with colonic disease (L2) and healthy controls. In contrast, we found significantly higher levels of alpha-defensins in the TI of children with UC compared to CD and controls. Reduced expression of Tcf-4 was observed exclusively in the duodenum and TI of CD patients with L1+L3 phenotype. We demonstrate significantly increased expression of HD5 and HD6 in the inflamed colon of IBD children (UC and CD) attributable to the presence of metaplastic Paneth cells.
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 a possibly impaired PC differentiation may lead to altered HD5 and HD6 expression at some stage of disease. Additionally, substantially increased expression of alpha-defensins in the inflamed colonic mucosa of children with IBD raises the question for their potential involvement in modulating inflammation in these patients.
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