Abstract
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 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. This exploratory study provided the first histological evidence that MAdCAM-1 and TNF-α could be upregulated in pediatric pouchitis and associated with disease severity, highlighting the pathological relevance of adult UC therapeutic targets in this setting.
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The datasets used and/or analyzed during the current study are available from the corresponding author (TY) upon reasonable request.
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Acknowledgements
We thank Ms. Mariko Nakamura, Kao Abe, Yukiko Suto, Kyoko Miyoshi, Chiho Noguchi, Saori Suto, Miyoko Suzuki, Sayaka Okada, and Harumi Kanai for their assistance with this study.
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The following authors conceived and designed the study: SO, EK, TY, HK, KS, and HS. The experiments were performed by SO, EK, TY, NG, KO, NS, HO, SM, TS, NO, GD, TO, AS, MSa, and MSu. The data were analyzed by SO, EK, TY, NG, KO, NS, HO, SM, TS, NO, GD, TO, AS, MSa, and MSu. The following authors wrote the paper: SO, EK, TY, HK, KS, and HS. Final confirmation of the manuscript was conducted by TY, HK, KS, and HS.
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Otake, S., Khorolgarav, E., Yokobori, T. et al. Therapeutic targets established in adult ulcerative colitis exhibit correlations with disease severity and pathological relevance in pediatric pouchitis. Sci Rep (2026). https://doi.org/10.1038/s41598-026-40173-7
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DOI: https://doi.org/10.1038/s41598-026-40173-7
