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Original article
Local barrier dysfunction identified by confocal laser endomicroscopy predicts relapse in inflammatory bowel disease
  1. R Kiesslich1,
  2. C A Duckworth2,
  3. D Moussata3,
  4. A Gloeckner1,
  5. L G Lim4,
  6. M Goetz1,
  7. D M Pritchard2,
  8. P R Galle1,
  9. M F Neurath5,
  10. A J M Watson6
  1. 1Medical Department, Johannes Gutenberg University of Mainz, Mainz, Germany
  2. 2Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, UK
  3. 3Department of Gastroenterology, Lyon Sud Hospital, Claude Bernard University, Pierre Benite, France
  4. 4Department of Gastroenterology and Hepatology, National University Health System, Yong Yoo Lin School of Medicine, National University of Singapore, Singapore
  5. 5Department of Medicine I, University of Erlangen-Nuremberg, Erlangen, Germany
  6. 6Faculty of Health, Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich UK
  1. Correspondence to Professor A J M Watson, Eliz Fry Bldg. 2.14, Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, UK; alastair.watson{at}uea.ac.uk

Abstract

Objectives Loss of intestinal barrier function plays an important role in the pathogenesis of inflammatory bowel disease (IBD). Shedding of intestinal epithelial cells is a potential cause of barrier loss during inflammation. The objectives of the study were (1) to determine whether cell shedding and barrier loss in humans can be detected by confocal endomicroscopy and (2) whether these parameters predict relapse of IBD.

Methods Confocal endomicroscopy was performed in IBD and control patients using intravenous fluorescein to determine the relationship between cell shedding and local barrier dysfunction. A grading system based on appearances at confocal endomicroscopy in humans was devised and used to predict relapse in a prospective pilot study of 47 patients with ulcerative colitis and 11 patients with Crohn's disease.

Results Confocal endomicroscopy in humans detected shedding epithelial cells and local barrier defects as plumes of fluorescein effluxing through the epithelium. Mouse experiments demonstrated inward flow through some leakage-associated shedding events, which was increased when luminal osmolarity was decreased. In IBD patients in clinical remission, increased cell shedding with fluorescein leakage was associated with subsequent relapse within 12 months after endomicroscopic examination (p<0.001). The sensitivity, specificity and accuracy for the grading system to predict a flare were 62.5% (95% CI 40.8% to 80.4%), 91.2% (95% CI 75.2 to 97.7) and 79% (95% CI 57.7 to 95.5), respectively.

Conclusions Cell shedding and barrier loss detected by confocal endomicroscopy predicts relapse of IBD and has potential as a diagnostic tool for the management of the disease.

  • Confocal laser endomicroscopy
  • mucosal healing
  • fluorescein
  • tight junction
  • barrier function
  • cell shedding
  • tumour necrosis factor
  • Crohn's Disease
  • ulcerative colitis
  • inflammatory bowel disease
  • colonoscopy
  • endoscopy
  • Barrett's metaplasia
  • Barrett's oesophagus
  • magnifying colonoscopy
  • apoptosis
  • colorectal metastases
  • colorectal cancer
  • gastrointestinal physiology
  • gut differentiation
  • gastrin
  • IBD basic research
  • cell death
  • IBD models

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

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Supplementary materials

Footnotes

  • RK and CAD share first authorship.

  • Parts of the study were presented at Digestive Disease Week 2009 at the plenary session and at Digestive Disease Week 2011.

  • Funding Wellcome Trust grant WT087768MA to AJMW and a grant from Association François Aupetit (AFA) to DM.

  • Competing interests RK has an unrestricted grant from Pentax Europe and has received instruments for free via Optiscan. All other authors have no competing interests.

  • Ethics approval The study was approved by the local ethical committee in Rheinland-Pfalz, Germany (No. 837.364.07).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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