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.
- coeliac disease
- intraepithelial lymphocytes
- ROC-curve analysis
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Contributors Forty-one pathologists and gastroenterologists participated in this study by contributing towards pathology and clinical data, discussion on study concept, statistical analysis and writing and revising the manuscript. The study was designed during the second consensus meeting incorporated in the International Course of Pathology in Bucharest. KR designed and coordinated the study, organised the second consensus meeting with help and support from GBe. He also collected the data and wrote the first draft of the manuscript. HM performed the first statistical analysis and contributed towards data interpretation. CH performed the second analysis and MNM rewrote the draft and revised the interpretation of data. MWJ and GH critically reviewed the manuscript and MWJ contributed with clinical and histology data. GBe provided data and co-organised the consensus meeting. MHD and JJG contributed with their data, critical revision, drafting and finalising the manuscript. ASr, AE, VV, UV, MD, ACa, ANB, CCi, MRN and LE contributed in the conceptualisation and design of the study, data collection and critical revision of the manuscript. BB, GBa, ABo, CCa, ACi, SF, MiF, MaF, AG, KG, SI, AM, SM, RM, CJM, IR, ASi and MRZ contributed with their pathology and clinical data and revision of the manuscript.
Competing interests None declared.
Ethics approval Research and development/audit departments of countries involved and the ethical committee of Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran under the following ethical number: IR.SBMU.RIGLD.REC.1395.87.
Provenance and peer review Not commissioned; externally peer reviewed.
Correction notice This article has been corrected since it published Online First. The affiliations for Sauid Ishaq, Masoud Sotoudeh and Stefano Ferrero have been updated.
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