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Roc-King Onwards: Intraepithelial Lymphocyte Counts, Distribution & Role in Coeliac Disease Mucosal Interpretation Publisher Pubmed



Rostami K1 ; Marsh MN2, 3 ; Johnson MW2 ; Mohaghegh H4 ; Heal C5 ; Holmes G6 ; Ensari A7 ; Aldulaimi D8 ; Bancel B9 ; Bassotti G10 ; Bateman A11 ; Becheanu G12 ; Bozzola A13 ; Carroccio A14 Show All Authors
Authors
  1. Rostami K1
  2. Marsh MN2, 3
  3. Johnson MW2
  4. Mohaghegh H4
  5. Heal C5
  6. Holmes G6
  7. Ensari A7
  8. Aldulaimi D8
  9. Bancel B9
  10. Bassotti G10
  11. Bateman A11
  12. Becheanu G12
  13. Bozzola A13
  14. Carroccio A14
  15. Catassi C15
  16. Ciacci C16
  17. Ciobanu A12
  18. Danciu M17
  19. Derakhshan MH18, 19
  20. Elli L20
  21. Ferrero S20
  22. Fiorentino M21
  23. Fiorino M14
  24. Ganji A22
  25. Ghaffarzadehgan K23
  26. Going JJ24
  27. Ishaq S25
  28. Mandolesi A15
  29. Mathews S1
  30. Maxim R17
  31. Mulder CJ26
  32. Neefjesborst A26
  33. Robert M27
  34. Russo I16
  35. Rostaminejad M4
  36. Sidoni A10
  37. Sotoudeh M19
  38. Villanacci V13
  39. Volta U21
  40. Zali MR4
  41. Srivastava A28
Show Affiliations
Authors Affiliations
  1. 1. Department of Gastroenterology and Pathology, Milton Keynes University Hospital, Milton Keynes, MK6 5LD, United Kingdom
  2. 2. Department of Gastroenterology, Luton and Dunstable University Hospital, Luton, United Kingdom
  3. 3. Wolfson College, University of Oxford, Oxford, United Kingdom
  4. 4. Gastroenterology and Liver Diseases Research Centre, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  5. 5. Centre for Biostatistics, Faculty of Biology, Academic Health Science Centre, University of Manchester, Manchester, United Kingdom
  6. 6. Department of Gastroenterology, Royal Derby Hospital, Derby, United Kingdom
  7. 7. Department of Pathology, Ankara University Medical School, Ankara, Turkey
  8. 8. Department of Gastroenterology, Warwick Hospital, Warwick, United Kingdom
  9. 9. Service de Pathologie, Centre de Biologie et Pathologie Groupe Hospitalier du Nord, Hospices Civils de Lyon, Lyon, France
  10. 10. University of Perugia Medical School, Perugia, Italy
  11. 11. Department of Cellular Pathology, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom
  12. 12. Department of Pathology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
  13. 13. Institute of Pathology Spedali Civili, Brescia, Italy
  14. 14. Internal Medicine and Pathology Unit, University of Palermo, Giovanni Paolo II Hospital, Sciacca, Italy
  15. 15. Department of Pediatrics and Surgical Pathology, Universita Politecnica delle Marche, Ancona, Italy
  16. 16. Department of Medicine and Surgery, Scuola Medica Salernitana, University of Salerno, Salerno, Italy
  17. 17. Department of Gastroenterology and Pathology, Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania
  18. 18. College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom
  19. 19. Digestive Disease Research Center, Tehran University Medical Science, Tehran, Iran
  20. 20. Center for Prevention and Diagnosis of Coeliac Disease and Pathology Unit, Fondazione IRCCS Ca' granda Ospedale Maggiore Policlinico, Milan, Italy
  21. 21. Department of Medical and Surgical Sciences, University of Bologna and Diagnostic and Experimental, University of Bologna, Bologna, Italy
  22. 22. Gastroenterology and Hepatology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
  23. 23. Pathology Department, Razavi Hospital, Mashhad, Iran
  24. 24. Department of Pathology, Southern General Hospital, Lanarkshire, United Kingdom
  25. 25. Dudley Group of Hospitals, Birmingham City University, Birmingham, United Kingdom
  26. 26. Department of Hepatogastroenterology and Pathology, Free University Medical Centre, Amsterdam, Netherlands
  27. 27. Department of Pathology and Medicine, Yale University School of Medicine, New Haven, United States
  28. 28. Department of Pathology, Brigham and Women's Hospital, Boston, United States

Source: Gut Published:2017


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. © Article author(s).