ROC-king onwards: intraepithelial lymphocyte counts, distribution & role in coeliac disease mucosal interpretation

Rostami, K. et al. (2017) ROC-king onwards: intraepithelial lymphocyte counts, distribution & role in coeliac disease mucosal interpretation. Gut, 66(12), pp. 2080-2086. (doi: 10.1136/gutjnl-2017-314297) (PMID:28893865) (PMCID:PMC5749338)

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Abstract

Objectives: Counting intraepithelial lymphocytes (IEL) is central to the histological diagnosis of coeliac disease (CD), but no definitive ‘normal’ IEL range has ever been published. In this multicentre study, receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off between normal and CD (Marsh III lesion) duodenal mucosa, based on IEL counts on >400 mucosal biopsy specimens. Design: The study was designed at the International Meeting on Digestive Pathology, Bucharest 2015. Investigators from 19 centres, eight countries of three continents, recruited 198 patients with Marsh III histology and 203 controls and used one agreed protocol to count IEL/100 enterocytes in well-oriented duodenal biopsies. Demographic and serological data were also collected. Results: The mean ages of CD and control groups were 45.5 (neonate to 82) and 38.3 (2–88) years. Mean IEL count was 54±18/100 enterocytes in CD and 13±8 in normal controls (p=0.0001). ROC analysis indicated an optimal cut-off point of 25 IEL/100 enterocytes, with 99% sensitivity, 92% specificity and 99.5% area under the curve. Other cut-offs between 20 and 40 IEL were less discriminatory. Additionally, there was a sufficiently high number of biopsies to explore IEL counts across the subclassification of the Marsh III lesion. Conclusion: Our ROC curve analyses demonstrate that for Marsh III lesions, a cut-off of 25 IEL/100 enterocytes optimises discrimination between normal control and CD biopsies. No differences in IEL counts were found between Marsh III a, b and c lesions. There was an indication of a continuously graded dose–response by IEL to environmental (gluten) antigenic influence.

Item Type:Articles
Additional Information:The Authors would like to thank Coeliac UK for making this study accessible by funding the open access publication fee.
Keywords:ROC-curve analysis, coeliac disease, intraepithelial lymphocytes.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Derakhshan, Dr Mohammad
Authors: Rostami, K., Marsh, M. N., Johnson, M. W., Mohaghegh, H., Heal, C., Holmes, G., Ensari, A., Aldulaimi, D., Bancel, B., Bassotti, G., Bateman, A., Becheanu, G., Bozzola, A., Carroccio, A., Catassi, C., Ciacci, C., Ciobanu, A., Danciu, M., Derakhshan, M. H., Elli, L., Ferrero, S., Fiorentino, M., Fiorino, M., Ganji, A., Ghaffarzadehgan, K., Going, J. J., Ishaq, S., Mandolesi, A., Mathews, S., Maxim, R., Mulder, C. J., Neefjes-Borst, A., Robert, M., Russo, I., Rostami-Nejad, M., Sidoni, A., Sotoudeh, M., Villanacci, V., Volta, U., Zali, M. R., and Srivastava, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Gut
Publisher:BMJ Publishing Group
ISSN:0017-5749
ISSN (Online):1468-3288
Published Online:11 September 2017
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Gut 66(12):2080-2086
Publisher Policy:Reproduced under a Creative Commons license

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