Optimizing intraepithelial lymphogram for celiac disease diagnosis in children: Cut‐off points and the role of bulb biopsies

Abstract The intraepithelial lymphogram, assessed by flow cytometry, has emerged as a valuable complementary tool for diagnosing celiac disease (CD). To optimize cutoff points for intraepithelial lymphocyte (IEL) subsets and to evaluate the diagnostic value of intraepithelial lymphogram in bulb and distal duodenal biopsies for active and potential CD in pediatric patients. This multicenter retrospective study included 190 pediatric patients (≤14 years old) who underwent duodenal biopsies for histological evaluation and flow cytometry. Patients were categorized as active CD ( n = 54), potential CD ( n = 69), and non‐CD controls ( n = 67). Total IELs, TcRγδ IELs, and sCD3 − IELs were quantified in bulb and distal duodenum biopsies. Cutoff points were optimized using ROC analysis. Agreement between cytometric patterns based on optimized and reference cutoffs was assessed using histological and serological criteria (Kappa coefficient). Sensitivity, specificity, and predictive values were evaluated for both biopsy sites. Active CD patients showed significantly increased total IELs and TcRγδ IELs, and decreased sCD3 − IELs in both anatomical regions. Optimized cutoff points for active CD were TcRγδ IELs >11.1% in the bulb and in the distal duodenum, sCD3 − IELs <6.4% in the bulb, and <8.5% in the distal duodenum. These cutoffs demonstrated stronger concordance with serological and histological findings than the reference values. Sensitivity improved when both anatomical regions were analyzed. In the potential CD group, a significant decrease in sCD3 − IELs was observed only in the bulb, where more patients exhibited a complete celiac lymphogram. Optimizing IEL subsets cutoff points and the inclusion of bulb biopsies enhances the diagnostic performance of intraepithelial lymphograms for active and potential CD in pediatric patients.