ROC-king onwards: intraepithelial lymphocyte counts, distribution & role in coeliac disease mucosal interpretation

Area of Science:

• Gastroenterology
• Histopathology
• Immunology

Background:

• Accurate diagnosis of coeliac disease (CD) relies on quantifying intraepithelial lymphocytes (IEL) in duodenal biopsies.
• A standardized normal range for IEL counts is currently lacking, hindering definitive histological diagnosis.

Purpose of the Study:

• To establish an optimal cut-off value for intraepithelial lymphocyte (IEL) counts to differentiate normal duodenal mucosa from Marsh III lesions indicative of coeliac disease (CD).

Main Methods:

• A multicentre study involving 19 centres analyzed over 400 duodenal biopsy specimens.
• Receiver operating characteristic (ROC) curve analysis was employed to determine the optimal IEL count threshold.
• IEL counts were standardized as IEL per 100 enterocytes.

Main Results:

• The mean IEL count was significantly higher in CD patients (54±18/100 enterocytes) compared to controls (13±8/100 enterocytes).
• ROC analysis identified an optimal cut-off of 25 IEL/100 enterocytes, achieving 99% sensitivity and 92% specificity.
• No significant differences in IEL counts were observed across Marsh III sublesions (a, b, c).

Conclusions:

• A threshold of 25 intraepithelial lymphocytes (IEL) per 100 enterocytes effectively discriminates between normal and coeliac disease (CD) duodenal biopsies with Marsh III lesions.
• The findings suggest a potential dose-response relationship between environmental antigenic influence (gluten) and IEL counts.