International Journal of Celiac Disease
ISSN (Print): 2334-3427 ISSN (Online): 2334-3486 Website: Editor-in-chief: Samasca Gabriel
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International Journal of Celiac Disease. 2016, 4(1), 4-6
DOI: 10.12691/ijcd-4-1-1
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Intraepithelial Lymphocyte Normal Cut-off Level in Celiac Disease: The Debate Continues

Aaron Lerner1, 2, and Torsten Matthias1

1AESKU.KIPP Institute, Wendelsheim, Germany

2B. Rappaport School of Medicine, Technion-Israel Institute of Technology, Haifa, Israel

Pub. Date: February 16, 2016

Cite this paper:
Aaron Lerner and Torsten Matthias. Intraepithelial Lymphocyte Normal Cut-off Level in Celiac Disease: The Debate Continues. International Journal of Celiac Disease. 2016; 4(1):4-6. doi: 10.12691/ijcd-4-1-1


The gold standard for diagnosis of celiac disease is positive serology confirmed by histological evidence of small intestinal biopsy damage as determined by the modified Marsh classification. Intraepithelial lymphocyte count has a pivotal importance in this grading criteria and the normal cut-off density has paramount importance in distinguishing between celiac disease and normal or false+ conditions. However its determination is problematic, complicated and far from being standardized. The localization along the villi or along the small bowel, the section thickness, the mode of detection and analysis, geoepidemiological influences, age dependency, associated infections or diseases and the strictness of the inclusions/exclusion criteria of the normal control group, all affect IEL density and normal cut-off levels. It is hoped that after standardization, the cut-off levels of IELs will better reflect the in-vivo reality to distinguish celiac disease from normal and associated conditions that affect intestinal IEL count.

intraepithelial lymphocyte celiac disease intestine diagnosis children

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[1]  Lerner A, Neidhöfer S, Matthias T. Serological markers and/or intestinal biopsies in the case-finding of celiac disease. International Journal of Celiac Disease. 2015;3:53-55.
[2]  Lerner A, Amon-Levin N, Shapiro Y, Gilbert B, Reuter S, Lava L, Shoenfeld Y. The thrombophilia network of autoantibodies in celiac disease. BMJ Medicine, 2013, 11; 89-95.
[3]  Lerner A. New Therapeutic Strategies for Celiac Disease. Autoimmune. Rev. 2010; 9:144-147.
[4]  Lerner A. Serological Diagnosis of Celiac Disease –Moving Beyond the Tip of the Iceberg. International Journal of Celiac Disease. 2014; 2:64-66.
[5]  Lerner A, Jeremias P, Matthias T. Outside of normal limits: false +/- anti TG2 autoantibodies. International Journal of Celiac Disease. 2015; 3:87-90.
[6]  Lerner A, Neidhöfer S, Matthias T. Transglutaminase 2 and anti transglutaminase 2 autoantibodies in celiac disease and beyond. Part B: Anti- Transglutaminase 2 autoantibodies: friends or enemies. Immunome Research , In Press, 2015.
[7]  Lerner A, Neidhöfer S, Jeremias P, Matthias T. The diversities between the neo-epitope and the IgA- tissue transglutaminase autoantibodies in celiac disease. In: Autoantigens, autoantibodies, autoimmunity. Volume 10th , Eds: K Conrad, Chan EKL, Andrade LEC, Steiner G, Pruijn GJM, Y Shoenfeld. Page 220-226, e-pub, 2015.
[8]  Jeremias P, Lerner A, Neidhöfer S, Matthias T. Industrial food additive microbial transglutaminase is immunogenic in children with celiac disease. 12th symposium on autoantibodies, 23-26.9.15, Dresden, Germany.
[9]  Freeman HJ. Small intestinal mucosal biopsies for case-finding in celiac disease. International Journal of Celiac Disease. 2015;3:50-52.
[10]  Siriweera EH, Qi Z, Yong JLC. Validity of Intraepithelial Lymphocyte Count in the Diagnosis of Celiac Disease: A Histopathological Study. Internat J celiac Disease. 2015; 3: 156-158.
[11]  Antonioli D. Coeliac disease :A progress report. Mod Pathol. 2003;6;342-346.
[12]  Dickson BC, Streutker CJ, Chetty R. Coeliac disease: an update for pathologists. J Clin Pathol. 2006;59:1008-1016.
[13]  Fernández-Bañares F, Carrasco A, García-Puig R wet al. Intestinal intraepithelial lymphocyte cytometric pattern is more accurate than subepithelial deposits of anti-tissue transglutaminase IgA for the diagnosis of celiac disease in lymphocytic enteritis. PLoS One. 2014;9:e101249.
[14]  De Andrés A, Camarero C, Roy G. Distal duodenum versus duodenal bulb: intraepithelial lymphocytes have something to say in celiac disease diagnosis. Dig Dis Sci. 2015;60:1004-1009.
[15]  Bednarska O, Ignatova S, Dahle C, Ström M. Intraepithelial lymphocyte distribution differs between the bulb and the second part of duodenum. BMC Gastroenterol. 2013;13:111-115.
[16]  Hammer ST, Greenson JK. The clinical significance of duodenal lymphocytosis with normal villus architecture. Arch Pathol Lab Med. 2013;137:1216-1219.
[17]  Camarero C, Leon F, Sanchez L, Asensio A, Roy G. Age-related variation of intraepithelial lymphocytes subsets in normal human duodenal mucosa. Dig Dis Sci. 2007;52:685-691.
[18]  Pellegrino S, Villanacci V, Sansotta N, et al. Redefining the intraepithelial lymphocytes threshold to diagnose gluten sensitivity in patients with architecturally normal duodenal histology. Aliment Pharmacol Ther. 2011;33:697-706.
[19]  Shmidt E, Smyrk TC, Boswell CL, Enders FT, Oxentenko AS. Increasing duodenal intraepithelial lymphocytosis found at upper endoscopy: time trends and associations. Gastrointest Endosc. 2014;80:105-111.
[20]  Guz-Mark A, Zevit N, Morgenstern S, Shamir R. Duodenal intraepithelial lymphocytosis is common in children without coeliac disease, and is not meaningfully influenced by Helicobacter pylori infection. Aliment Pharmacol Ther. 2014;39:1314-1320.
[21]  Losurdo G, Piscitelli D, Giangaspero A, et al. Evolution of nonspecific duodenal lymphocytosis over 2 years of follow-up. World J Gastroenterol. 2015;21:7545-7552.
[22]  Lerner A, Matthias T. Rheumatoid arthritis-celiac disease relationship: joints get that gut feeling. Autoimm Rev. 2015:14:1038-1047.
[23]  Chang F, Mahadeva U, Deere H. Pathological and clinical significance of increased intraepithelial lymphocytes (IELs) in small bowel mucosa. APMIS. 2005;113:385-99.