Redefining the intraepithelial lymphocytes threshold to diagnose gluten sensitivity in patients with architecturally normal duodenal histology

Aliment Pharmacol Ther. 2011 Mar;33(6):697-706. doi: 10.1111/j.1365-2036.2011.04578.x. Epub 2011 Jan 23.


Background: Accuracy of intraepithelial lymphocytes counts for diagnosing mild enteropathy coeliac disease in absence of villous atrophy can be limited by inappropriate controls included in the studies.

Aim: To determine the diagnostic accuracy of intraepithelial lymphocytes counts utilising controls lacking HLA coeliac disease-associated alleles.

Methods: Intraepithelial lymphocytes counting at villus tip and per 100 enterocytes was performed at haematoxylin and eosin (H&E) and CD3-stainings in: 29 cases (21 with potential coeliac disease and 8 affected by latent coeliac disease) representing the patient population and 14 noncoeliac controls lacking HLA-DQ2/DQ8 alleles.

Results: Threshold (mean+2 s.d.) of duodenal intraepithelial lymphocytes at villus tip and per 100 enterocytes in noncoeliac controls was respectively: 3.5 and 18 at H&E, 3.2 and 17 following CD3-staining. Considering the whole patient population, the sensitivity of tip intraepithelial lymphocytes in detecting mild enteropathy coeliac disease was 90% (95% CI=72.6-97.8) both at H&E and CD3-stainings. The sensitivity of intraepithelial lymphocytes per 100 enterocytes was 93% (95% CI=77.2-99.2) both at H&E and CD3-staining. Specificity of both intraepithelial lymphocytes counts was 100% (95% CI=76.8-100). Using a threshold of 25 intraepithelial lymphocytes per 100 enterocytes could miss 59% of cases at H&E and 48% following CD3-staining.

Conclusions: Intraepithelial lymphocytes counts are diagnostic feasible tools to detect mild enteropathy coeliac disease. Threshold of duodenal intraepithelial lymphocytes may be lower than currently accepted.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biopsy
  • Celiac Disease / diagnosis*
  • Celiac Disease / pathology
  • Child
  • Child, Preschool
  • Duodenum / pathology*
  • Enterocytes / pathology
  • Female
  • Histocompatibility Testing
  • Humans
  • Intestinal Mucosa / pathology*
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Retrospective Studies
  • Sensitivity and Specificity
  • Young Adult