Discriminant value of IEL counts and distribution pattern through the spectrum of gluten sensitivity: a simple diagnostic approach
Intraepithelial lymphocytosis (IELosis) with or without villous abnormality is a characteristic feature of gluten sensitivity (GS) including celiac disease (CD) and non-celiac-GS, although various conditions may also be associated with IELosis. In order to distinguish GS from the other causes of IELosis, a threshold for IEL counts is necessary. We aimed to determine a cut-off value for IELs and monitor its value in the spectrum of GS in a large cohort. For this purpose, the duodenal biopsies from four groups of individuals including Types 1 (n = 88) and 3 (n = 92) CD, non-CD IELosis (n = 112), and control (n = 82) cases, all strictly defined by their clinical, laboratory, and serologic features, were evaluated. The number of IELs/100 enterocytes and their distribution pattern on H&E- and CD3-immunostained sections were assessed for each group. Kruskal-Wallis test and ROC curve analysis for discriminant value were employed for statistics. The IEL counts showed an increasing trend through the spectrum of mucosal pathology including controls (12.06; 21.40), non-CD IELosis (28.62; 39.46), Type 1 CD (49.27; 60.15), and Type 3 CD (58.53; 71.74) both on H&E- and CD3-immunostained sections, respectively (p < 0.001). ROC analysis revealed 20.5 on H&E and 28.5 on CD3 as the IEL cut-off values with a sensitivity of 95.9 and 87.7% and a specificity of 98.8% and 93.9%, respectively, for controls. IELs showed a diffuse distribution pattern per biopsy piece and per villus (90.9%, 100%, respectively) in nearly all of Type 1 CD cases (p < 0.001). An IEL cut-off value of 20.5 on H&E together with a diffuse distribution pattern seem to be the most discriminant features for the diagnosis of CD, even for the milder forms of the disease.
KeywordsCeliac disease Intraepithelial lymphocytosis Discriminant analysis
Ayca Kirmizi and Arzu Ensari designed the study, generated the study groups, made the histopathological analysis, criticized the results, and wrote, edited, and reviewed the manuscript. Cagdas Kalkan, İrfan Soykan, and Hulya Cetinkaya constitued the clinical part of the study groups. Seher Yuksel photographed the histopathological slides of the cases. Berna Savas evaluated the results of the study and criticized the discussion part. Zeynep Gencturk made the whole statistical analysis. All authors gave final approval for publication.
Compliance with ethical standards
This retrospective study has been approved by the Institutional Review Board. See supplementary material for the decision in Turkish and translated version in English.
Conflict of interest
The authors declare that they have no conflict of interest.
- 3.Rostami K, Aldulaimi D, Holmes G, Johnson MW, Robert M, Srivastava A, Fléjou JF, Sanders DS, Volta U, Derakhshan MH, Going JJ, Becheanu G, Catassi C, Danciu M, Materacki L, Ghafarzadegan K, Ishaq S, Rostami-Nejad M, Peña AS, Bassotti G, Marsh MN, Villanacci V (2015) Microscopic enteritis: Bucharest consensus. World J Gastroenterol 21(9):2593–2604. https://doi.org/10.3748/wjg.v21.i9.2593 CrossRefPubMedPubMedCentralGoogle Scholar
- 16.Biagi F, Luinetti O, Campanella J, Klersy C, Zambelli C, Villanacci V, Lanzini A, Corazza GR (2004) Intraepithelial lymphocytes in the villous tip: do they indicate potential coeliac disease? J Clin Pathol 57(8):835–839. https://doi.org/10.1136/jcp.2003.013607 CrossRefPubMedPubMedCentralGoogle Scholar
- 18.Rostami K, Marsh MN, Johnson MW, 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 MH, Elli L, Ferrero S, Fiorentino M, Fiorino M, Ganji A, Ghaffarzadehgan K, Going JJ, Ishaq S, Mandolesi A, Mathews S, Maxim R, Mulder CJ, Neefjes-Borst A, Robert M, Russo I, Rostami-Nejad M, Sidoni A, Sotoudeh M, Villanacci V, Volta U, Zali MR, 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 CrossRefPubMedPubMedCentralGoogle Scholar
- 19.Bhatnagar S, Gupta SD, Mathur M, Phillips AD, Kumar R, Knutton S, Unsworth J, Lock B, Natchu UCM, Mukhopadhyaya S, Saini S, Bhan MK (2005) Celiac disease with mild to moderate histologic changes is a common cause of chronic diarrhea in Indian children. J Pediatr Gastroenterol Nutr 41(2):204–209CrossRefPubMedGoogle Scholar
- 21.Kirmizi A (2017) Small intestine, anatomy and histology. In: Carneiro F, Chaves P, Ensari A (ed) Pathology of the Gastrointestinal Tract, 1st edn. Springer, pp 641-644Google Scholar
- 22.Pellegrino S, Villanacci V, Sansotta N et al (2011) Redefining the intraepithelial lymphocytes threshold to diagnose gluten sensitivity in patients with architecturally normal duodenal histology. Aliment Pharmacol Ther 33:697–706. https://doi.org/10.1111/j.1365-2036.2011.04578 CrossRefPubMedGoogle Scholar