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Increased Epithelial Gap Density in the Noninflamed Duodenum of Children With Inflammatory Bowel Diseases
Deenaz Zaidi1, Michael Bording-Jorgensen, Hien Q Huynh
1*Department of Pediatrics †Centre of Excellence for Gastrointestinal Inflammation and Immunity Research (CEGIIR) ‡Department of Physiology §Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada ||University of Arkansas for Medical Sciences, Little Rock, AR.
Insights
Pediatric inflammatory bowel diseases (IBD) show increased duodenal epithelial gaps, a potential early sign. This barrier defect in IBD patients, including ulcerative colitis (UC), may precede or occur independently of inflammation.
Area of Science:
- Gastroenterology
- Pediatric Gastroenterology
- Immunology
Background:
- Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), commonly affect children with unknown causes.
- The epithelial lining plays a crucial role in IBD pathogenesis.
- Increased epithelial cell extrusion, indicated by epithelial gaps, has been observed in adult CD patients.
Purpose of the Study:
- To compare duodenal epithelial gap density in pediatric IBD patients versus non-IBD controls.
- To investigate the correlation between epithelial gaps, inflammation, and disease activity in pediatric IBD.
- To identify potential underlying mechanisms contributing to epithelial barrier dysfunction in pediatric IBD.
Main Methods:
- Probe-based confocal laser endomicroscopy was used to quantify duodenal epithelial gap density in 26 pediatric IBD patients (16 CD, 10 UC) and 17 non-IBD controls.
- Epithelial gaps were correlated with inflammatory markers (CRP, ESR), disease activity indices, and intraepithelial lymphocytes.
- Analysis of 10 inflammatory cytokines and A20 (TNFAIP3) expression in duodenal and ileal biopsies.
Main Results:
- Significantly higher duodenal epithelial gap density was found in pediatric IBD patients, including those with UC.
- In UC patients, elevated IL-2 and IL-8 were noted in duodenal biopsies, but no correlation was found between epithelial gaps and inflammation markers or disease activity.
- In CD patients, C-reactive protein (CRP) positively correlated with epithelial gaps; A20 expression was unchanged.
Conclusions:
- Duodenal epithelial gaps are increased in pediatric IBD patients, including UC, independent of inflammation.
- Altered duodenal epithelial barrier function appears to be a systemic feature of pediatric IBD.
- These findings suggest that epithelial barrier defects may be a primary or early event in pediatric IBD, not solely a consequence of inflammation.
Objectives:
Inflammatory bowel diseases (IBD) present commonly in childhood, with unknown etiology, but an important role for the epithelial lining is suggested. Epithelial cell extrusion, measured by counting gaps between epithelial cells, is higher in adult patients with Crohn disease (CD) than in controls. Our objectives were to compare epithelial gaps in the duodenum of IBD and non-IBD pediatric patients, to study the correlation between epithelial gaps, inflammation, and disease activity, and identify potential mechanisms.
Methods:
Epithelial gap density of the duodenum was evaluated using probe-based confocal laser endomicroscopy in 26 pediatric patients with IBD (16 CD, 10 ulcerative colitis [UC]) and 17 non-IBD controls during endoscopy. Epithelial gaps were correlated with serum inflammatory markers, disease activity indices, and intraepithelial lymphocytes. A panel of 10 inflammatory cytokines and expression of TNFAIP3 (A20; inhibits NF-κβ-induced inflammation) were analyzed in duodenal and ileal biopsies.
Results:
Confocal imaging showed significantly higher epithelial gap density in patients with IBD, including UC. Interleukin (IL)-2 and IL-8 were higher in duodenal but not ileal biopsies of patients with UC. No significant correlation was present between C-reactive protein, erythrocyte sedimentation rate, disease activity indices, and epithelial gaps in patients with UC. In patients with CD, C-reactive protein positively correlated with epithelial gaps. A20 expression in the duodenum was unchanged among non-IBD and IBD cases.
Conclusions:
Duodenal epithelial gaps are increased in pediatric patients with IBD (including UC) but are unrelated to inflammation. This suggests that altered epithelial barrier is an important systemic feature of pediatric IBD and is not only secondary to inflammation.
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