Roc-king onwards: Intraepithelial lymphocyte counts, distribution & role in coeliac disease mucosal interpretation

Kamran Rostami*, Michael N. Marsh, Matt W. Johnson, Hamid Mohaghegh, Calvin Heal, Geoffrey Holmes, Arzu Ensari, David Aldulaimi, Brigitte Bancel, Gabrio Bassotti, Adrian Bateman, Gabriel Becheanu, Anna Bozzola, Antonio Carroccio, Carlo Catassi, Carolina Ciacci, Alexandra Ciobanu, Mihai Danciu, Mohammad H. Derakhshan, Luca ElliStefano Ferrero, Michelangelo Fiorentino, Marilena Fiorino, Azita Ganji, Kamran Ghaffarzadehgan, James J. Going, Sauid Ishaq, Alessandra Mandolesi, Sherly Mathews, Roxana Maxim, Chris J. Mulder, Andra Neefjes-Borst, Marie Robert, Ilaria Russo, Mohammad Rostami-Nejad, Angelo Sidoni, Masoud Sotoudeh, Vincenzo Villanacci, Umberto Volta, Mohammad R. Zali, Amitabh Srivastava

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)2080-2086
Number of pages7
JournalGut
Volume66
Issue number12
DOIs
Publication statusPublished - 2017

Cite this

Rostami, K., Marsh, M. N., Johnson, M. W., Mohaghegh, H., Heal, C., Holmes, G., ... Srivastava, A. (2017). Roc-king onwards: Intraepithelial lymphocyte counts, distribution & role in coeliac disease mucosal interpretation. Gut, 66(12), 2080-2086. https://doi.org/10.1136/gutjnl-2017-314297