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Published in: Digestive Diseases and Sciences 7/2016

01-07-2016 | Original Article

Epithelial Cell Extrusion Zones Observed on Confocal Laser Endomicroscopy Correlates with Immunohistochemical Staining of Mucosal Biopsy Samples

Authors: Julia J. Liu, Theresa M. Kay, Elisabeth M. Davis, Yuefei Lou, Dina Kao, Brian Claggett, Richard N. Fedorak, Randall T. Irvin

Published in: Digestive Diseases and Sciences | Issue 7/2016

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Abstract

Background and Aims

The density of epithelial cell extrusion zones in the intestinal lining, also known as gap density (number of gaps/1000 epithelial cells counted), can be quantitated using probe-based confocal laser endomicroscopy (pCLE). Gap density has been reported to be higher than normal in both inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) patients. Epithelial cells destined for extrusion from the intestinal surface would stain positive for either activated caspase-1 or caspase-3 on mucosal biopsy samples. The aim of this study was to determine whether epithelial gap density on pCLE correlates with quantitative analysis of activated caspase staining of mucosal biopsy samples from patients.

Methods

We obtained pCLE images and biopsy samples of the terminal ileum during colonoscopies of healthy controls and patients with either IBD or IBS. The pCLE images and biopsy samples were blindly analyzed for gap density and for cells staining positive for activated caspases, respectively. The degree of correlation was determined using nonparametric statistical tests.

Results

The median results were 10 gaps/1000 cells counted for controls versus 33 gaps/1000 cells counted for chronic intestinal disorder patients (p = 0.02). Activated caspase staining showed 13 positive cells/1000 epithelial cells counted versus 26 positive cells/1000 epithelial cells counted, respectively (p = 0.02), thus showing a strong correlation with a Spearman’s coefficient ρ of 0.61 (strong correlation for ρ = 0.4–0.75, p = 0.01).

Conclusions

Intestinal epithelial gap density via pCLE correlated strongly with quantitative analysis of immunohistochemical staining of mucosal biopsy samples.
Literature
1.
go back to reference Kiesslich R, Goetz M, Angus EM, et al. Identification of epithelial gaps in human small and large intestine by confocal endomicroscopy. Gastroenterology. 2007;133:1769–1778.CrossRefPubMed Kiesslich R, Goetz M, Angus EM, et al. Identification of epithelial gaps in human small and large intestine by confocal endomicroscopy. Gastroenterology. 2007;133:1769–1778.CrossRefPubMed
2.
go back to reference Liu JJ, Wong K, Thiesen AL, et al. Increased epithelial gaps in the small intestines of patients with inflammatory bowel disease: density matters. Gastrointest Endosc. 2011;73:1174–1180.CrossRefPubMed Liu JJ, Wong K, Thiesen AL, et al. Increased epithelial gaps in the small intestines of patients with inflammatory bowel disease: density matters. Gastrointest Endosc. 2011;73:1174–1180.CrossRefPubMed
3.
go back to reference Turcotte JF, Kao D, Mah SJ, et al. Breaks in the wall: increased gaps in the intestinal epithelium of irritable bowel syndrome patients identified by confocal laser endomicroscopy (with videos). Gastrointest Endosc. 2013;77:624–630.CrossRefPubMed Turcotte JF, Kao D, Mah SJ, et al. Breaks in the wall: increased gaps in the intestinal epithelium of irritable bowel syndrome patients identified by confocal laser endomicroscopy (with videos). Gastrointest Endosc. 2013;77:624–630.CrossRefPubMed
4.
go back to reference Turcotte JF, Wong K, Mah SJ, et al. Increased epithelial gaps in the small intestine are predictive of hospitalization and surgery in patients with inflammatory bowel disease. Clin Transl Gastroenterol. 2012;3:e19.CrossRefPubMedPubMedCentral Turcotte JF, Wong K, Mah SJ, et al. Increased epithelial gaps in the small intestine are predictive of hospitalization and surgery in patients with inflammatory bowel disease. Clin Transl Gastroenterol. 2012;3:e19.CrossRefPubMedPubMedCentral
5.
go back to reference Karstensen JG, Saftoiu A, Brynskov J, et al. Confocal laser endomicroscopy: a novel method for prediction of relapse in Crohn’s disease. Endoscopy. 2016;48:364–372.PubMed Karstensen JG, Saftoiu A, Brynskov J, et al. Confocal laser endomicroscopy: a novel method for prediction of relapse in Crohn’s disease. Endoscopy. 2016;48:364–372.PubMed
6.
go back to reference Shavrov A, Kharitonova AY, Claggett B, et al. A pilot study of the predictive value of probe-based confocal laser endomicroscopy for relapse in pediatric inflammatory bowel disease patients. J Pediatr Gastroenterol Nutr. 2015. doi:10.1097/MPG.0000000000001022. Shavrov A, Kharitonova AY, Claggett B, et al. A pilot study of the predictive value of probe-based confocal laser endomicroscopy for relapse in pediatric inflammatory bowel disease patients. J Pediatr Gastroenterol Nutr. 2015. doi:10.​1097/​MPG.​0000000000001022​.
7.
go back to reference Fritscher-Ravens A, Schuppan D, Ellrichmann M, et al. Confocal endomicroscopy shows food-associated changes in the intestinal mucosa of patients with irritable bowel syndrome. Gastroenterology. 2014;147:1012e4–1020e4.CrossRef Fritscher-Ravens A, Schuppan D, Ellrichmann M, et al. Confocal endomicroscopy shows food-associated changes in the intestinal mucosa of patients with irritable bowel syndrome. Gastroenterology. 2014;147:1012e4–1020e4.CrossRef
8.
go back to reference Liu JJ, Rudzinski JK, Mah SJ, et al. Epithelial gaps in a rodent model of inflammatory bowel disease: a quantitative validation study. Clin Transl Gastroenterol. 2011;2:e3.CrossRefPubMedPubMedCentral Liu JJ, Rudzinski JK, Mah SJ, et al. Epithelial gaps in a rodent model of inflammatory bowel disease: a quantitative validation study. Clin Transl Gastroenterol. 2011;2:e3.CrossRefPubMedPubMedCentral
9.
go back to reference Mayhew TM, Myklebust R, Whybrow A, et al. Epithelial integrity, cell death and cell loss in mammalian small intestine. Histol Histopathol. 1999;14:257–267.PubMed Mayhew TM, Myklebust R, Whybrow A, et al. Epithelial integrity, cell death and cell loss in mammalian small intestine. Histol Histopathol. 1999;14:257–267.PubMed
10.
go back to reference Rosenblatt J, Raff MC, Cramer LP. An epithelial cell destined for apoptosis signals its neighbors to extrude it by an actin- and myosin-dependent mechanism. Curr Biol. 2001;11:1847–1857.CrossRefPubMed Rosenblatt J, Raff MC, Cramer LP. An epithelial cell destined for apoptosis signals its neighbors to extrude it by an actin- and myosin-dependent mechanism. Curr Biol. 2001;11:1847–1857.CrossRefPubMed
11.
go back to reference Watson AJ, Chu S, Sieck L, et al. Epithelial barrier function in vivo is sustained despite gaps in epithelial layers. Gastroenterology. 2005;129:902–912.CrossRefPubMed Watson AJ, Chu S, Sieck L, et al. Epithelial barrier function in vivo is sustained despite gaps in epithelial layers. Gastroenterology. 2005;129:902–912.CrossRefPubMed
12.
go back to reference Liu JJ, Davis EM, Wine E, et al. Epithelial cell extrusion leads to breaches in the intestinal epithelium. Inflamm Bowel Dis. 2013;19:912–921.CrossRefPubMed Liu JJ, Davis EM, Wine E, et al. Epithelial cell extrusion leads to breaches in the intestinal epithelium. Inflamm Bowel Dis. 2013;19:912–921.CrossRefPubMed
13.
go back to reference Kiesslich R, Duckworth CA, Moussata D, et al. Local barrier dysfunction identified by confocal laser endomicroscopy predicts relapse in inflammatory bowel disease. Gut. 2012;61:1146–1153.CrossRefPubMed Kiesslich R, Duckworth CA, Moussata D, et al. Local barrier dysfunction identified by confocal laser endomicroscopy predicts relapse in inflammatory bowel disease. Gut. 2012;61:1146–1153.CrossRefPubMed
14.
go back to reference Lim LG, Neumann J, Hansen T, et al. Confocal endomicroscopy identifies loss of local barrier function in the duodenum of patients with Crohn’s disease and ulcerative colitis. Inflamm Bowel Dis. 2014;20:892–900.CrossRefPubMed Lim LG, Neumann J, Hansen T, et al. Confocal endomicroscopy identifies loss of local barrier function in the duodenum of patients with Crohn’s disease and ulcerative colitis. Inflamm Bowel Dis. 2014;20:892–900.CrossRefPubMed
15.
go back to reference Gunther C, Martini E, Wittkopf N, et al. Caspase-8 regulates TNF-alpha-induced epithelial necroptosis and terminal ileitis. Nature. 2011;477:335–339.CrossRefPubMedPubMedCentral Gunther C, Martini E, Wittkopf N, et al. Caspase-8 regulates TNF-alpha-induced epithelial necroptosis and terminal ileitis. Nature. 2011;477:335–339.CrossRefPubMedPubMedCentral
Metadata
Title
Epithelial Cell Extrusion Zones Observed on Confocal Laser Endomicroscopy Correlates with Immunohistochemical Staining of Mucosal Biopsy Samples
Authors
Julia J. Liu
Theresa M. Kay
Elisabeth M. Davis
Yuefei Lou
Dina Kao
Brian Claggett
Richard N. Fedorak
Randall T. Irvin
Publication date
01-07-2016
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 7/2016
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-016-4154-x

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