Digestive Diseases and Sciences

, Volume 60, Issue 4, pp 1004–1009 | Cite as

Distal Duodenum Versus Duodenal Bulb: Intraepithelial Lymphocytes Have Something to Say in Celiac Disease Diagnosis

  • Ana De Andrés
  • Cristina Camarero
  • Garbiñe Roy
Original Article


Background and Aim

After clinical screening and the serological test, many patients still require a duodenal biopsy for celiac disease diagnosis. Mild histological lesions, unspecific findings and patchiness are frequent outcomes of this mandatory diagnostic tool, thus complicating clinical decisions.


We analyzed the lymphoid components [number of total intraepithelial lymphocytes (IELs), TcR-γδ and CD3IELs] of the duodenal epithelium by flow cytometry in samples obtained from bulb and distal duodenum during upper gastrointestinal endoscopies performed for diagnostic purposes.


IEL counts and IEL subset distribution (IEL lymphogram) remain invariant along duodenal mucosa revealing a specific profile (immunophenotype) that characterizes either a healthy mucosa or a celiac mucosa. The celiac immunophenotype persists regardless of the biopsy’s anatomical location or the corresponding histological findings.


We propose the IEL lymphogram by flow cytometry as an immunological parameter to discern celiac condition from healthy mucosa. This obviates not only misinterpretation of minor histological changes, but also patchiness and the concerns about the location and number of biopsies.


Celiac disease Immunophenotype Patchy lesion Flow cytometry 



Celiac disease


Endomysial antibodies


Gluten-free diet


IgA anti-transglutaminase-2 auto-antibodies



Supported by grant MEC I+D SAF2006-01403 from the Spanish Ministry for Education and Science.

Conflict of interest



  1. 1.
    Green PH, Cellier C. Celiac disease. N Engl J Med. 2007;357:1731–1743.CrossRefPubMedGoogle Scholar
  2. 2.
    Jabri B, Kasarda DD, Green PH. Innate and adaptive immunity: the yin and yang of celiac disease. Immunol Rev. 2005;206:219–231.CrossRefPubMedGoogle Scholar
  3. 3.
    Dewar DH, Ciclitira P. Clinical features and diagnosis of celiac disease. Gastroenterology. 2005;128:S19–S24.CrossRefPubMedGoogle Scholar
  4. 4.
    Hill ID, Dirks MH, Liptak GS, et al. Guideline for the diagnosis and treatment of celiac disease in children: recommendations of the North American Society for Pediatric gastroenterology, hepatology and nutrition. J Pediatr Gastroenterol Nutr. 2005;40:1–19.CrossRefPubMedGoogle Scholar
  5. 5.
    Rostom A, Murray JA, Kagnoff MF. American Gastroenterological Association (AGA) Institute technical review on the diagnosis and management of celiac disease. Gastroenterology. 2006;131:1981–2002.CrossRefPubMedGoogle Scholar
  6. 6.
    Schuppan D. Current concepts of celiac disease pathogenesis. Gastroenterology. 2000;119:234–242.CrossRefPubMedGoogle Scholar
  7. 7.
    Giersiepen K, Lelgeman M, Stuhldreher N, et al. Accuracy of diagnostic antibody tests for coeliac disease in children: summary of an evidence report. J Pediatr Gastroenterol Nutr. 2012;54:229–241.CrossRefPubMedGoogle Scholar
  8. 8.
    European Society of Paediatric Gastroenterology and Nutrition. Revised criteria for diagnosis of coeliac disease. Arch Dis Child. 1990;65:909–911.CrossRefGoogle Scholar
  9. 9.
    Rashid M, MacDonald A. Importance of duodenal bulb biopsies in children for diagnosis of celiac disease in clinical practice. BMC Gastroenterol. 2009;9:78.Google Scholar
  10. 10.
    Husby S, Koletzko S, Korponay-Szabó IR, et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr. 2012;54:136–160.CrossRefPubMedGoogle Scholar
  11. 11.
    Holm K, Mäki M, Savilahti E, et al. Intraepithelial gamma delta T-cell-receptor lymphocytes and genetic susceptibility to coeliac disease. Lancet. 1992;339:1500–1503.CrossRefPubMedGoogle Scholar
  12. 12.
    Savilahti E, Arato A, Verkasalo M. Intestinal gamma/delta receptor-bearing T lymphocytes in celiac disease and inflammatory bowel disease in children. Constant increase in celiac disease. Pediatr Res. 1990;28:579–581.CrossRefPubMedGoogle Scholar
  13. 13.
    Spencer J, MacDonald TT, Diss TC, et al. Changes in intraepithelial lymphocyte subpopulations in coeliac disease and enteropathy associated T cell lymphoma (malignant histiocytosis of the intestine). Gut. 1989;30:339–346.CrossRefPubMedCentralPubMedGoogle Scholar
  14. 14.
    Koskinen O, Collin P, Lindfors K, et al. Usefulness of small-bowel mucosal transglutaminase-2 specific autoantibody deposits in the diagnosis and follow-up of celiac disease. J Clin Gastroenterol. 2010;44:483–488.PubMedGoogle Scholar
  15. 15.
    Camarero C, Eiras P, Asensio A, et al. Intraepithelial lymphocytes and coeliac disease: permanent changes in CD3−/CD7+ and T cell receptor gd subsets studied by flow cytometry. Acta Paediatr. 2000;89:285–290.PubMedGoogle Scholar
  16. 16.
    Bonamico M, Thanasi E, Mariani P, et al. Duodenal bulb biopsies in celiac disease: a multicenter study. J Pediatr Gastroenterol Nutr. 2008;47:618–622.CrossRefPubMedGoogle Scholar
  17. 17.
    Tjon JM, van Bergen J, Koning F. Celiac disease: how complicated can it get? Immunogenetics. 2010;62:641–651.CrossRefPubMedCentralPubMedGoogle Scholar
  18. 18.
    Prasad KK, Thapa BR, Nain CK, et al. Assessment of the diagnostic value of duodenal bulb histology in patients with celiac disease, using multiple biopsy sites. J Clin Gastroenterol. 2009;43:307–311.CrossRefPubMedGoogle Scholar
  19. 19.
    Zawahir S, Safta A, Fasano A. Pediatric celiac disease. Curr Opin Pediatr. 2009;21:655–660.CrossRefPubMedGoogle Scholar
  20. 20.
    Hopper AD, Cross SS, Sanders DS. Patchy villous atrophy in adult patients with suspected gluten-sensitive enteropathy: is a multiple duodenal biopsy strategy appropriate? Endoscopy. 2008;40:219–224.CrossRefPubMedGoogle Scholar
  21. 21.
    Bonamico M, Mariani P, Thanasi E, et al. Patchy villous atrophy of the duodenum in chidhood celiac disease. J Pediatr Gastroenterol Nutr. 2004;38:204–207.CrossRefPubMedGoogle Scholar
  22. 22.
    Leon F. Flow cytometry of intestinal intraepithelial lymphocytes in celiac disease. J Immunol Methods. 2011;363:177–186.CrossRefPubMedGoogle Scholar
  23. 23.
    Camarero C, León F, Sánchez L, et al. Age-related variation of intraepithelial lymphocytes subsets in normal human duodenal mucosa. Dig Dis Sci. 2007;52:685–691.CrossRefPubMedGoogle Scholar
  24. 24.
    Eiras P, Roldán E, Camarero C, et al. Flow cytometry description of a novel CD3−/CD7+ intraepithelial lymphocyte subset in human biopsies: potential diagnostic value in coeliac disease. Cytometry. 1998;34:95–102.CrossRefPubMedGoogle Scholar
  25. 25.
    Green PH, Jabri B. Coeliac disease. Lancet. 2003;362:383–391.CrossRefPubMedGoogle Scholar
  26. 26.
    Halstensen TS, Scott H, Fausa O, et al. Gluten stimulation of coeliac mucosa in vitro induces activation (CD25) of lamina propria CD4+ T cells and macrophages but no crypt-cell hyperplasia. Scand J Immunol. 1993;38:581–590.CrossRefPubMedGoogle Scholar
  27. 27.
    Leon F, Eiras P, Roy G, et al. Intestinal intraepithelial lymphocytes and anti-transglutaminase in a screening algorithm for coeliac disease. Gut. 2002;50:740–741.CrossRefPubMedCentralPubMedGoogle Scholar
  28. 28.
    Oberhuber G, Granditsch G, Vogelsang H. The histopathology of coeliac disease: time for a standardized report for pathologists. Eur J Gastroenterol Hepatol. 1999;11:1185–1194.CrossRefPubMedGoogle Scholar
  29. 29.
    Arranz E, Ferguson A. Intestinal antibody pattern of celiac disease: occurrence in patients with normal jejunal biopsy histology. Gastroenterology. 1993;104:1263–1272.PubMedGoogle Scholar
  30. 30.
    Fasano A, Catassi C. Clinical practice. Celiac disease. N Engl J Med. 2012;367:2419–2426.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Ana De Andrés
    • 1
  • Cristina Camarero
    • 2
  • Garbiñe Roy
    • 1
  1. 1.Department of ImmunologyHospital Universitario Ramón y Cajal de MadridMadridSpain
  2. 2.Department of Paediatric GastroenterologyHospital Universitario Ramón y CajalMadridSpain

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