The Utility and Validation of Intraepithelial Lymphocyte Count in Duodenal Biopsies in A Tertiary Care Centre in South India
Keywords:
Intraepithelial lymphocytes, duodenum, celiac disease, immunohistochemistry
Abstract
Background: Intraepithelial lymphocytes (IELs) are seen in between the epithelial cells in small and large intestine with the functions of immune surveillance and activation. Increased IELs can be the sole histological finding in latent celiac disease (CD). Aims: To study the utility and clinical relevance of IELs in diagnosing non-neoplastic lesions of duodenum and to determine a cut off for IEL to differentiate CD from other conditions. Materials & methods: This was a prospective descriptive study. Duodenal biopsies from 106 patients with symptoms of malabsorption were studied. Informed written consent was taken. Clinical details were collected. Histomorphological parameters were studied on hematoxylin and eosin stained sections. Intraepithelial lymphocyte counts were done on CD3, CD4 and CD8 IHC stained sections. Statistical analysis was done using IBM- SPSS software version 21. P value <0.05 was considered statistically significant. The threshold score of IELs with maximum sensitivity and specificity was validated using the Receiver operator characteristic curve to distinguish CD from non-celiac disease conditions. Results: We studied 101 duodenal biopsies. Our spectrum included 16 patients of CD (15.8%), 15 of autoimmune duodenitis (14%), 13 of nutritional deficiency associated duodenitis (12.8%), 5 of infectious duodenitis (5%) and 41 patients of non-specific duodenitis (40.6%). The threshold levels were 5/20 villous tip IELs, 24 IELs/100 enterocytes on H& E and >31 IELs by CD3 IHC staining. Conclusion: Our study proposes IEL counts of >31/100 enterocytes in CD3 IHC staining to be significant in South Indian population to differentiate CD from other conditions.References
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2. Hayat M, Cairns A, Dixon MF, O’Mahony S. Quantitation of intraepithelial lymphocytes in human duodenum: what is normal? J Clin Pathol. 2002;55:393–4.
3.Veress B, Franzén L, Bodin L, Borch K. Duodenal intraepithelial lymphocyte‐count revisited. Scand J Gastroenterol. 2004;39:138-44.
4..Cabanne A, Vázquez H, Argonz J, et al. Clinical utility of counting intraepithelial lymphocytes in celiac disease intestinal mucosa. Acta Gastroenterol Latinoam. 2007;37:20-8.
5. Chang F, Mahadeva U, Deere H. Pathological and clinical significance of increased intraepithelial lymphocytes IELs in small bowel mucosa. APMIS. 2005;113:385-9
6. Kalhan S, Joseph P, Sharma S, Dubey S, Dudani S, Dixit M. Comparative study of histopathological Marsh grading with clinical and serological parameters in celiac iceberg of north India. Indian J Pathol Microbiol.2011;54:279-83.
7. GS Datta. Pathology of celiac disease: a brief review. Trop Gastroenterol 2013;34:207-26.
8. Sher KS, Frasar RC, Wicks AC, Mayberry JF. High risk of celiac disease in Punjabis : Epidemiological study in the south Asian and European populations of Leicestershire. Digestion. 1993;54:178–82.
9. Sood A, Midha V, Sood N, Avasthi G, Sehgal A. Prevalence of celiac disease among school children in Punjab, North India. J Gastroenterol Hepatol.2006;21:1622-5.
10. Bhattacharya M, Dubey AP, Mathur NB. Prevalence of celiac disease in north Indian children. Indian Pediatr. 2009;46:415-7.
11.Tatar G, Elsurer R, Simsek H, et al. Screening of tissue transglutaminase antibody in healthy blood donors for celiac disease screening in the Turkish population. Dig Dis Sci. 2004;49:1479–84.
12. Ertekin V, Selimoğlu MA, Kardaş F, Aktaş E. Prevalence of celiac disease in Turkish children. J Clin Gastroenterol.2005;39:689–91.
13. Akbari MR, Mohammadkhani A, Fakheri H, et al. Screening of the adult population in Iran for coeliac disease: comparison of the tissue-transglutaminase antibody and anti-endomysial antibody tests. Eur J Gastroenterol Hepatol. 2006;18:1181–6.
14. Sood A, Midha V, Sood N, Malhotra V. Adult celiac disease in northern India. Indian J Gastroenterol. 2003;22:124-6.
15.Abu-Zekry M, Kryszak D, Diab M, Catassi C, Fasano A. Prevalence of celiac disease in Egyptian children disputes the east-west agriculture-dependent spread of the disease. J Pediatr Gastroenterol Nutr.2008;47:136–40.
16. Sachdev A, Srinivasan V, Maheswary S, Mohan H, Ashish B, Singh LS. Adult onset celiac disease in north India. Trop Gastroenterol. 2002;23:117–9.
17.Ben Hariz M, Kallel-Sellami M, Kallel L, et al. Prevalence of celiac disease in Tunisia: mass-screening study in school children. Eur J Gastroenterol Hepatol. 2007;19:687–94.
18. Ramakrishna BS. Celiac disease: can we avert the impending epidemic in India? Indian J Med Res. 2011;133:5-8
19. Yachha SK, Poddar U. Celiac disease in India. Indian J Gastroenterol. 2007;26:230–7.
20. Ganesh R, Suresh N, Sathiyasekaran M. Celiac disease, still an uncommon problem in Tamilians? Indian J Gastroenterol. 2009;28:189.
21. Shamir R, Lerner A, Shinar E,et al. The use of a single serological marker underestimates the prevalence of celiac disease in Israel: a study of blood donors. Am J Gastroenterol.2002;97:2589–94.
22.Balasubramanian P, Badhe BA, Ganesh RN , Panicker LC, Mohan P. Morphologic Spectrum of Duodenal Biopsies in Malabsorption: A Study from Southern India. J Clin Diagn Res. 2017;11:17-21.
23. 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.
24. Brown I, Mino-Kenudson M, Deshpande V, Lauwers GY. Intraepithelial Lymphocytosis in Architecturally Preserved Proximal Small Intestinal Mucosa. An Increasing Diagnostic Problem With a Wide Differential Diagnosis. Arch Pathol Lab Med. 2006;130:1020-5.
25.Kakar S, Nehra V, Murray JA, Dayharsh GA, Burgart LJ. Significance of intraepithelial lymphocytosis in small bowel biopsy samples with normal mucosal architecture. Am J Gastroenterol. 2003;98:2027–33.
26. Wahab PJ, Crusius JB, Meijer JW, Mulder CJ. Gluten challenge in borderline gluten sensitive enteropathy. Am J Gastroenterol. 2001;96:1464–9.
27. Williams L, Dew MJ, Murray LA, Williams DA. Are routine duodenal biopsies taken at the time of an upper GI endoscopy clinically useful? Gasteroenterol Today. 2001;11:73-76.
28. Biagi F, Luinetti O, Campanella J, et al. Intraepithelial lymphocytes in the villous tip: do they indicate potential coeliac disease? J Clin Pathol. 2004;57:835–9.
29.Järvinen TT, Collin P, Rasmussen M, et al. Villous tip intraepithelial lymphocytes as markers of early‐stage coeliac disease. Scand J Gastroenterol. 2004; 39:428–33.
30. Nasseri-Moghaddam S, Mofid A, Nouraie M, et al. The normal range of duodenal intraepithelial lymphocytes. Arch Iran Med. 2008;11:136-42.
Published
08-11-2019
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