Redefining the intraepithelial lymphocytes threshold to diagnose gluten sensitivity in patients with architecturally normal duodenal histology
Related Experiment Video
Updated: Jun 5, 2026

Recognition of Epidermal Transglutaminase by IgA and Tissue Transglutaminase 2 Antibodies in a Rare Case of Rhesus Dermatitis
Published on: December 15, 2011
S Pellegrino1, V Villanacci, N Sansotta
1Regional Celiac Center, Pad. NI, University Hospital G. Martino, via Consolare Valeria 1, Messina, Italy. fumonero@inwind.it
Insights
Accurate intraepithelial lymphocytes counts can diagnose mild coeliac disease enteropathy. Lowering the threshold for duodenal intraepithelial lymphocytes may improve detection rates in patients.
Area of Science:
- Gastroenterology
- Immunology
- Pathology
Background:
- Diagnosing mild coeliac disease enteropathy without villous atrophy is challenging.
- Previous studies may have used inappropriate controls, limiting the accuracy of intraepithelial lymphocytes (IELs) counts.
Purpose of the Study:
- To assess the diagnostic accuracy of IELs counts.
- To utilize controls lacking coeliac disease-associated HLA alleles (HLA-DQ2/DQ8).
Main Methods:
- IELs were counted at the villus tip and per 100 enterocytes using H&E and CD3 staining.
- The study included 29 patients with potential or latent coeliac disease and 14 controls lacking HLA-DQ2/DQ8.
Main Results:
- Normal IEL thresholds in controls were established (e.g., 3.5 at villus tip/H&E).
- High sensitivity (90-93%) and specificity (100%) were observed for IELs counts in detecting mild coeliac disease enteropathy.
- A threshold of 25 IELs/100 enterocytes could miss a significant percentage of cases.
Conclusions:
- IELs counts are feasible diagnostic tools for mild coeliac disease enteropathy.
- The current accepted threshold for duodenal IELs may need to be lowered for improved diagnostic accuracy.
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.
Related Concept Videos
Histology of the Small Intestine
The intestinal lining features transverse folds called circular folds, each housing fingerlike projections known as intestinal villi. These villi are covered by a layer of simple columnar epithelium, also referred to as...
Inflammatory Bowel Disease III: Crohn's Disease
Inflammatory Bowel Disease III: Diagnostic Studies and Management I-Nutritional Therapy
Diagnostic studies
A colonoscopy is the definitive screening test, distinguishing ulcerative colitis from other colon diseases with similar symptoms. During a colonoscopy test, inflamed mucosa with exudate ulcerations can be observed, and biopsies are taken to determine the histologic characteristics of the colonic...
