Mucosal Addressin Cell Adhesion Molecule 1 Expression Reflects Mucosal Inflammation and Subsequent Relapse in Patients with Ulcerative Colitis

Author:

Uchiyama Kazuhiko1,Takagi Tomohisa12,Mizushima Katsura3,Hirai Yasuko3,Asaeda Kohei1,Sugaya Takeshi4,Kajiwara-Kubota Mariko1,Kashiwagi Saori1,Minagawa, Yuki1,Hotta Yuma1,Tanaka Makoto1,Inoue Ken1,Katada Kazuhiro1,Kamada Kazuhiro1,Ishikawa Takeshi1,Yasuda Hiroaki1,Konishi Hideyuki1,Kishimoto Mitsuo5,Naito Yuji3ORCID,Itoh Yoshito1

Affiliation:

1. Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine , Kajiicho Hirokoji Kawaramachi Kamigyo-ku, Kyoto , Japan 602-8566

2. Department for Medical Innovation and Translational Medical Science, Graduate School of Medical Science, Kyoto Prefectural University of Medicine , 465 Kajiicho Hirokoji Kawaramachi Kamigyo-ku, Kyoto , Japan 602-8566

3. Department of Human Immunology and Nutrition Science, Kyoto Prefectural University of Medicine , 465 Kajiicho Hirokoji Kawaramachi Kamigyo-ku, Kyoto , Japan 602-8566

4. Medical Regulatory Science, Kyoto Prefectural University of Medicine , 465 Kajiicho Hirokoji Kawaramachi Kamigyo-ku, Kyoto , Japan 602-8566

5. Department of Surgical Pathology, Kyoto City Hospital , Kyoto , Japan 604-8845

Abstract

Abstract Background and Aims Mucosal addressin cell adhesion molecule 1 [MAdCAM-1] is upregulated in the vascular endothelium of the colonic mucosa in ulcerative colitis [UC]. Although the association between MAdCAM-1 expression and mucosal inflammation has been discussed, the association with the clinical course of UC patients has not been reported. In this study we investigated not only the association between mucosal MAdCAM-1 expression and mucosal inflammation, but also its association with subsequent relapse in UC patients with clinical remission. Methods Eighty UC patients in remission who visited Kyoto Prefectural University of Medicine for follow-up for 2 years were included. Biopsy samples were collected during colonoscopy, and transcriptional expression levels of UC-related cytokines and MAdCAM-1 were quantified using real-time polymerase chain reaction. MAdCAM-1 mRNA expression and protein expression by immunohistochemistry were compared in patients who subsequently relapsed and those who remained in remission and were examined in relation to endoscopic findings, histological activity and cytokine expression. Results MAdCAM-1 expression was correlated with endoscopic severity, and significantly elevated in histologically active mucosa than inactive mucosa. Furthermore, MAdCAM-1 expression levels were closely correlated with those of several cytokines. MAdCAM-1 mRNA and protein expression were significantly higher in the relapse group than in the remission group, indicating that MAdCAM-1 expression in the mucosa is already elevated in UC patients in clinical remission who subsequently relapse. Conclusions MAdCAM-1 expression in the colonic mucosa of UC patients is related to mucosal inflammation and subsequent relapse; it may serve as a marker for both relapse and therapeutic effectiveness in UC.

Funder

Ministry of Agriculture, Forestry and Fisheries

Japan Society for the Promotion of Science

Publisher

Oxford University Press (OUP)

Subject

Gastroenterology,General Medicine

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