Natural history and characterization of intestinal fibrosis in pediatric Crohn’s Disease

This thesis investigates pediatric inflammatory bowel disease (IBD), focusing on the incidence, phenotype, and fibrosis in Crohn's disease (CD). A population-based study compared very early-onset IBD (VEO-IBD, <6 years) and early-onset IBD (EO-IBD, 6–16 years), finding a stable incidence of VEO-IBD and a significant increase in EO-IBD over time. This difference suggests a genetic basis for VEO-IBD, while the rise in EO-IBD may be linked to environmental factors. VEO-IBD present higher rates of rectal and colonic involvements, distinguishing it from EO-IBD.

Intestinal fibrosis, a major complication of pediatric CD, contributes to long-term morbidity through strictures, requiring surgical intervention even in children. Despite its clinical importance, fibrosis remains poorly characterized in pediatric CD. Hence, four ER stress protein disulfide isomerases distributions have been characterized in association with inflammation and fibrosis within the intestinal epithelium. AGR2, BiP, and ERP44 show different associations with inflammation and fibrosis, with potentials as biomarkers or therapeutic targets. PDIA6 is upregulated in CD but not correlated with fibrosis, suggesting a different role in the disease process.

By combining epidemiology, phenotypic characterization, and molecular mechanisms, this thesis documents pediatric IBD fibrosis and ER stress proteins, with potential implications for improving disease management and interventions.