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An Intravital Microscopy-Based Approach to Assess Intestinal Permeability and Epithelial Cell Shedding Performance
Published on: December 3, 2020
Intestinal barrier dysfunction and differential CLDN8 and MUC1 expression in vedolizumab responsiveness among
N A Shahabudin1, R A Raja Ali2,3,4, G C Tan5
1Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia.
Introduction:
Vedolizumab (VDZ) is a biologic therapy targeting ulcerative colitis (UC) and Crohn's disease (CD) patients. However, response rates vary, potentially due to intestinal barrier dysfunction. This study aimed to investigate the ultrastructural characteristics and expression of genes related to the intestinal barrier in inflammatory bowel disease patients receiving VDZ therapy.
Materials And Methods:
A prospective cohort study was conducted at Universiti Kebangsaan Malaysia Medical Centre, recruiting UC and CD patients treated with VDZ, with follow-up at 6 months. Colonic biopsies were taken from responders and non-responders, alongside 10 healthy controls for comparison. Messenger RNA levels of MUC1, CLDN8, and OCLN were quantified using qPCR. Tissue sections were examined for tight junctions, gap junctions, and desmosomes using transmission electron microscopy. Barrier permeability was tested through barrier assay using a nano silver particle translocation assay, and the findings were analysed using inductively coupled plasma-mass spectrometry (ICP-MS).
Results:
Among the 25 patients (14 UC, 11 CD), responders showed significantly increase in CLDN8 and MUC1 expressions, while reduced OCLN expression compared to non-responders. Non-responders had wider tight and gap junctions. Additionally, responders displayed lower nano silver particle permeability than non-responders and healthy controls.
Conclusion:
Intestinal barrier dysfunction, evidenced by differential intestinal barrier gene expression and ultrastructural alterations, may contribute to the lack of response to VDZ therapy, particularly in biological-naïve CD patients. These findings underscore the critical role of intestinal barrier integrity in therapeutic responsiveness to VDZ in IBD patients.
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