Peripheral and Intestinal T-regulatory Cells are Upregulated in Children with Inflammatory Bowel Disease at Onset of Disease

ABSTRACT

Background/Aims: To determine the proportion of T-regulatory cells (CD4⁺CD25^highFOXP3⁺ cells) in peripheral blood and the number of FOXP3⁺ cells in intestinal mucosa of children with inflammatory bowel disease (IBD), and to verify whether these parameters correlate with the activity of the disease.

Material and methods: 24 patients newly diagnosed for IBD were included in the study: ulcerative colitis (UC; n = 13) and Crohn’s disease (CD; n = 11). Seventeen healthy controls (HC) and 16 patients with irritable bowel syndrome (IBS) served as a control group for peripheral and intestinal Tregs assessment, respectively. The disease activity was assessed by Pediatric Ulcerative Colitis Activity Index (PUCAI) and Pediatric Crohn’s Disease Activity Index (PCDAI). Quantification of regulatory T cells of CD4⁺CD25^highFOXP3⁺ phenotype in peripheral blood was based on three-color flow cytometry. Mucosal Tregs represented by FOXP3⁺ cells were evaluated using immunohistochemistry.

Results: Median proportion of CD4⁺CD25^highFOXP3⁺ cells among CD4⁺ T cells in peripheral blood (5.1%, range 1.7–84% vs. 4.3%, range 2–8.1%, p = 0.023) and median number of intestinal FOXP3+ cells (115.33 per high-power field, hpf, range 39.33–375.67 vs. 10.16 per hpf, range 5–30, p = 0.0001) were significantly higher in children with IBD than in the controls. The proportion of circulating Tregs and the number of intestinal FOXP3+ cells did not correlate with clinical activity of the disease, as well as with endoscopic and histopathologic scoring. No significant correlation was found between the percentage of peripheral CD4+CD25^highFOXP3+ cells and the number of intestinal FOXP3+cells.

Conclusions: Children with IBD likely do not present with a quantitative deficiency of circulating and intestinal Tregs at the moment of diagnosis.