Therapeutic targets established in adult ulcerative colitis exhibit correlations with disease severity and pathological relevance in pediatric pouchitis

Pediatric pouchitis has no established treatment strategy, and management is particularly challenging in recurrent or antibiotic-refractory cases. Tumor necrosis factor alpha (TNF-α) and mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) are established and emerging therapeutic targets, respectively, in adult ulcerative colitis (UC) and pouchitis; however, their expression profiles and clinical relevance in pediatric pouchitis remain unclear. Therefore, we evaluated the pathological and clinical significance of TNF-α and MAdCAM-1 in pediatric patients with pouchitis. We performed immunohistochemical analysis of surgically resected ileal tissues and subsequent pouch biopsy specimens obtained from 10 pediatric patients with UC. Paired pouchitis biopsies were collected during both active (high pouchitis disease activity index, PDAI) and improved (low PDAI) phases. TNF-α, MAdCAM-1, and immune cell markers (CD68, CD163, and CD8) in the mucosal stroma were quantitatively assessed using HALO image analysis. Compared with baseline ileal tissues, pouchitis specimens showed increased MAdCAM-1-positive vasculature and infiltration of CD68- and CD163-positive cells. In paired specimens, MAdCAM-1, TNF-α, and CD68 expression was significantly reduced in low-PDAI tissues. MAdCAM-1 and TNF-α expression was positively correlated with inflammatory cell infiltration. As the first demonstration of MAdCAM-1 and TNF-α upregulation in pediatric pouchitis and their association with disease severity, this study highlights the pathological relevance of adult UC therapeutic targets for pediatric pouchitis.