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

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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 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.
Original languageEnglish
Article numberizab059
Pages (from-to)1719-1730
Number of pages12
JournalInflammatory Bowel Diseases
Volume27
Issue number11
Early online date21 May 2021
DOIs
Publication statusPublished - Nov 2021

Keywords

  • RNA-sequencing
  • endocytoscope
  • histological healing
  • mucosal healing
  • noninvasive markers

ASJC Scopus subject areas

  • Immunology and Allergy
  • Gastroenterology

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