Ultra-high Magnification Endocytoscopy and Molecular Markers for Defining Endoscopic and Histologic Remission in Ulcerative Colitis-An Exploratory Study to Define Deep Remission.

Marietta Iacucci,Samuel C L Smith,John Williams,Louisa Jeffery,Uday N Shivaji,Rosanna Cannatelli,Olga Maria Nardone,Subrata Ghosh,Animesh Acharjee,Alina Bazarova,Georgios Gkoutos,Davide Zardo

doi:10.1093/ibd/izab059

Abstract

BackgroundEndoscopic 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.MethodsPatients 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 Robarts (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.ResultsEndocytoscope 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 α) 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.ConclusionsEndocytoscopy 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.

Highlights

Achieving mucosal healing (MH) is considered to be a primary target in the treatment of inflammatory bowel disease (IBD).[1,2,3] Mucosal healing increasingly incorporates both endoscopic remission (ER) and histologic remission (HR)
Correlations of Endocytoscopy and Histology (NHI and RHI) Scores in ulcerative colitis (UC) The ECS total score had very strong correlation with HR as defined by Nancy Histological Index (NHI) r = 0.86 and RHI r = 0.89
Whereas ECS total score correlated weakly with Mayo endoscopic score (MES) r = 0.28

Summary

Introduction

Achieving mucosal healing (MH) is considered to be a primary target in the treatment of inflammatory bowel disease (IBD).[1,2,3] Mucosal healing increasingly incorporates both endoscopic remission (ER) and histologic remission (HR). RNA-seq analysis identified gene expressions shared between ECSS, RHI, or NHI defined healing.

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