Iacucci, Marietta, Jeffery, Louisa, Acharjee, Animesh ORCID: 0000-0003-2735-7010, Nardone, Olga Maria ORCID: 0000-0002-9554-4785, Zardo, Davide, Smith, Samuel C. L., Bazarova, Alina, Cannatelli, Rosanna, Shivaji, Uday N., Williams, John ORCID: 0000-0002-0357-5454, Gkoutos, Georgios ORCID: 0000-0002-2061-091X and Ghosh, Subrata ORCID: 0000-0002-1713-7797 (2021). Ultra-high Magnification Endocytoscopy and Molecular Markers for Defining Endoscopic and Histologic Remission in Ulcerative Colitis - An Exploratory Study to Define Deep Remission. Inflamm. Bowel Dis., 27 (11). S. 1719 - 1731. CARY: OXFORD UNIV PRESS INC. ISSN 1536-4844

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Abstract

Background: Endoscopic and histological remission are both important treatment goals in patients with ulcerative colitis (UC). We aimed to define cellular architecture, expression of molecular markers, and their correlation with endoscopic scores assessed by ultra-high magnification endocytoscopy (ECS) and histological scores. Methods: Patients with UC (n = 29) were prospectively recruited. The correlation among ECS score (ECSS), Mayo endoscopic score (MES), and histological scores were determined. Area under curve were plotted to determine the best thresholds for ECSS that predicted histological remission by Roberts (RHI) and Nancy Histological Index (NHI). Soluble analytes relevant to inflammation were measured in serum and mucosal culture supernatants using ProcartaPlex Luminex assays and studied by partial least square discriminant analysis and logistic model. Mucosal RNA sequencing and bioinformatics analysis were performed to define differentially expressed genes/pathways. Results: Endocytoscope scoring system correlated strongly with RHI (r = 0.89; 95% CI, 0.51-0.98) and NHI (r = 0.86; 95% CI, 0.42-0.98) but correlated poorly with MES (r = 0.28; 95% CI, 0.27-0.70). We identified soluble brain-derived neurotrophic factors (BDNF), macrophage inflammatory proteins (MIP-1 alpha) and soluble vascular cell adhesion molecule 1 (sVCAM-1) predicted histological remission. Mucosal biopsy cultures also identified sVCAM-1 associated with healed mucosa. RNA-seq analysis identified gene expressions shared between ECSS, RHI, or NHI defined healing. A number of gene expressions and pathways were identified including inflammation and metabolic and tumor suppressors that discriminated healed from nonhealed mucosa. Conclusions: Endocytoscopy represents an interesting tool that may sit between endoscopy and histology-but closer to the latter-identifying gene expression markers and pathways that are also identified by histology.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Iacucci, MariettaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jeffery, LouisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Acharjee, AnimeshUNSPECIFIEDorcid.org/0000-0003-2735-7010UNSPECIFIED
Nardone, Olga MariaUNSPECIFIEDorcid.org/0000-0002-9554-4785UNSPECIFIED
Zardo, DavideUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Smith, Samuel C. L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bazarova, AlinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cannatelli, RosannaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shivaji, Uday N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Williams, JohnUNSPECIFIEDorcid.org/0000-0002-0357-5454UNSPECIFIED
Gkoutos, GeorgiosUNSPECIFIEDorcid.org/0000-0002-2061-091XUNSPECIFIED
Ghosh, SubrataUNSPECIFIEDorcid.org/0000-0002-1713-7797UNSPECIFIED
URN: urn:nbn:de:hbz:38-588229
DOI: 10.1093/ibd/izab059
Journal or Publication Title: Inflamm. Bowel Dis.
Volume: 27
Number: 11
Page Range: S. 1719 - 1731
Date: 2021
Publisher: OXFORD UNIV PRESS INC
Place of Publication: CARY
ISSN: 1536-4844
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
INFLAMMATORY-BOWEL-DISEASE; REPAIR; GOALS; STAGE; GENEMultiple languages
Gastroenterology & HepatologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/58822

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