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

doi:10.1093/ibd/izab059

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. 2021 Oct 20;27(11):1719-1730. doi: 10.1093/ibd/izab059.

Authors

Marietta Iacucci^{1

2

3}, Louisa Jeffery¹, Animesh Acharjee^{4

5

6}, Olga Maria Nardone¹, Davide Zardo⁷, Samuel C L Smith¹, Alina Bazarova⁸, Rosanna Cannatelli¹, Uday N Shivaji^{1

3}, John Williams^{4

5}, Georgios Gkoutos^{4

5

6

9}, Subrata Ghosh^{1

2

3

10}

Affiliations

¹ Institute of Immunology & Immunotherapy University of Birmingham, Birmingham, UK.
² NIHR Wellcome Trust Clinical Research Facilities University Hospitals Birmingham NHS Trust, University of Birmingham, Birmingham, UK.
³ NIHR Biomedical Research Centre, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
⁴ Institute of Cancer and Genomic Sciences, Centre for Computational Biology, University of Birmingham, Birmingham, UK.
⁵ Institute of Translational Medicine, University of Birmingham, Birmingham, UK.
⁶ NIHR Surgical Reconstruction and Microbiology Research Centre, University Hospital Birmingham, Birmingham.
⁷ University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
⁸ Institute for Biological Physics, University of Cologne, Cologne, Germany.
⁹ MRC Health Data Research UK (HDR), Birmingham, UK.
¹⁰ APC Microbiome Ireland, College of Medicine and Health, University College Cork, Cork, Ireland.

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 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.

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 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.

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.

Keywords: RNA-sequencing; endocytoscope; histological healing; mucosal healing; noninvasive markers.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers* / analysis
Colitis, Ulcerative* / diagnosis
Colitis, Ulcerative* / genetics
Colonoscopy
Endoscopy, Gastrointestinal
Humans
Inflammation
Intestinal Mucosa / chemistry
Remission Induction
Severity of Illness Index

Substances

Biomarkers