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Gut. 2017 Dec;66(12):2080-2086. doi: 10.1136/gutjnl-2017-314297. Epub 2017 Sep 11.

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

Author information

1
Department of Gastroenterology and Pathology, Milton Keynes University Hospital, Milton Keynes, UK.
2
Department of Gastroenterology, Luton and Dunstable University Hospital, Luton, UK.
3
Wolfson College, University of Oxford, Oxford, UK.
4
Gastroenterology and Liver Diseases Research Centre, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, The Islamic Republic of Iran.
5
Centre for Biostatistics, Faculty of Biology, Academic Health Science Centre, University of Manchester, Manchester, UK.
6
Department of Gastroenterology, Royal Derby Hospital, Derby, UK.
7
Department of Pathology, Ankara University Medical School, Ankara, Turkey.
8
Department of Gastroenterology, Warwick Hospital, Warwick, UK.
9
Service de Pathologie, Centre de Biologie et Pathologie Groupe Hospitalier du Nord, Hospices Civils de Lyon, Lyon, France.
10
University of Perugia Medical School, Perugia, Italy.
11
Department of Cellular Pathology, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
12
Department of Pathology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
13
Institute of Pathology Spedali Civili, Brescia, Italy.
14
Internal Medicine and Pathology Unit, University of Palermo, Giovanni Paolo II Hospital, Sciacca, Italy.
15
Department of Pediatrics and Surgical Pathology, Università Politecnica delle Marche, Ancona, Italy.
16
Department of Medicine and Surgery, Scuola Medica Salernitana, University of Salerno, Salerno, Italy.
17
Departments of Gastroenterology and Pathology, Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania.
18
College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
19
Digestive Disease Research Center, Tehran University Medical Science, Tehran, Iran.
20
Center for Prevention and Diagnosis of Coeliac Disease and Pathology Unit, Fondazione IRCCS Ca' granda Ospedale Maggiore Policlinico, Milano, Italy.
21
Department of Medical and Surgical Sciences, University of Bologna and Diagnostic and Experimental, University of Bologna, Bologna, Italy.
22
Gastroenterology and Hepatology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
23
Pathology Department, Razavi Hospital, Mashhad, Iran.
24
Department of Pathology, Southern General Hospital, Lanarkshire, UK.
25
Dudley group of Hospitals, Birmingham City University, Birmingham, UK.
26
Department of Hepatogastroenterology and Pathology, Free University Medical Centre, Amsterdam, The Netherlands.
27
Department of Pathology and Medicine, Yale University School of Medicine, New Haven, USA.
28
Department of Pathology, Brigham & Women's Hospital, Boston, USA.

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.

KEYWORDS:

ROC-curve analysis; coeliac disease; intraepithelial lymphocytes

PMID:
28893865
PMCID:
PMC5749338
DOI:
10.1136/gutjnl-2017-314297
[Indexed for MEDLINE]
Free PMC Article

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