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Background and Aims   Nonceliac gluten sensitivity (NCGS) is a gluten-related emerging condition. Since few data about NCGS histopathology is available, we assessed the markers of lymphocyte and innate immunity activation.Materials and Methods   We retrieved duodenal biopsy samples of patients with NCGS diagnosis according to the Salerno criteria. We selected specimens of positive (seropositive celiac disease/Marsh 1-2 stage) and negative (normal microscopic picture) controls. Immunohistochemistry for CD3 (intraepithelial lymphocytes-IELs), CD4 (T helper lymphocytes), CD8 (T cytotoxic lymphocytes), and CD1a/CD117 (Langerhans/mast cells) was performed. ANOVA plus Bonferroni's tests were used for statistical analysis.Results   Twenty NCGS, 16 celiac disease, and 16 negative controls were selected. CD3 in NCGS were higher than negative controls and lower than celiac disease (18.5 ± 6.4, 11.9 ± 2.8, and 40.8 ± 8.1 IELs/100 enterocytes;  p  < 0.001). CD4 were lower in NCGS than controls and celiac disease (31.0 ± 22.1, 72.5 ± 29.5, and 103.7 ± 15.7 cells/mm 2 ;  p  < 0.001). CD8 in NCGS were similar to negative controls, but lower than celiac disease (14.0 ± 7.4 and 34.0 ± 7.1 IELs/100 enterocytes,  p  < 0.001). CD117 were higher in NCGS than celiac disease and negative controls (145.8 ± 49.9, 121.3 ± 13.1, and 113.5 ± 23.4 cells/mm 2 ;  p  = 0.009).Conclusions   The combination of CD4 and CD117, as well as IEL characterization, may be useful to support a clinical diagnosis of NCGS.

T Helper Lymphocyte and Mast Cell Immunohistochemical Pattern in Nonceliac Gluten Sensitivity