Intraepithelial lymphocytosis (IELosis) with or without villous abnormality is a characteristic feature of gluten sensitivity (GS) including celiac disease (CD) and non-celiac-GS, although various conditions may also be associated with IELosis. In order to distinguish GS from the other causes of IELosis, a threshold for IEL counts is necessary. We aimed to determine a cut-off value for IELs and monitor its value in the spectrum of GS in a large cohort. For this purpose, the duodenal biopsies from four groups of individuals including Types 1 (n = 88) and 3 (n = 92) CD, non-CD IELosis (n = 112), and control (n = 82) cases, all strictly defined by their clinical, laboratory, and serologic features, were evaluated. The number of IELs/100 enterocytes and their distribution pattern on H&E- and CD3-immunostained sections were assessed for each group. Kruskal-Wallis test and ROC curve analysis for discriminant value were employed for statistics. The IEL counts showed an increasing trend through the spectrum of mucosal pathology including controls (12.06; 21.40), non-CD IELosis (28.62; 39.46), Type 1 CD (49.27; 60.15), and Type 3 CD (58.53; 71.74) both on H&E- and CD3-immunostained sections, respectively (p < 0.001). ROC analysis revealed 20.5 on H&E and 28.5 on CD3 as the IEL cut-off values with a sensitivity of 95.9 and 87.7% and a specificity of 98.8% and 93.9%, respectively, for controls. IELs showed a diffuse distribution pattern per biopsy piece and per villus (90.9%, 100%, respectively) in nearly all of Type 1 CD cases (p < 0.001). An IEL cut-off value of 20.5 on H&E together with a diffuse distribution pattern seem to be the most discriminant features for the diagnosis of CD, even for the milder forms of the disease.
Keywords: Celiac disease; Discriminant analysis; Intraepithelial lymphocytosis.