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

Abstract

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/mm2; 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/mm2; 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.

Novel steps forward in the histopathology of non-celiac gluten sensitivity

“…Therefore, histopathology could represent a very appealing field of study. In this regard, we recently demonstrated, by immunohistochemistry, a rise in CD117+ cells in the lamina propria of patients with NCGS [4]. CD117 may identify mast cells; consequently, this result seems to be in agreement with that of Zanini et al, who found, in most cases, an increase in eosinophil count (more than five eosinophils in the lamina propria per high power field) when compared to the control group, where this finding was absent.…”

Novel steps forward in the histopathology of non-celiac gluten sensitivity, authors’ reply

“…We thank the authors for agreeing on many of the histopathological and clinical points that result from our experience, partially confirmed in their publication [2], and for their letter of comment when they write Bsupport an additional hypothesis about NCGS pathogenesis: an allergic intolerance to foods other than wheat.T he interesting point of this publication is that it highlights the number of mast cells (CD117+) as a marker of NCGS. In our opinion, the elevated number of mast cells is due to the increased number of eosinophils, which is a common feature of NCGS patients describe in our study [1].…”

Extra-intestinal manifestations of non-celiac gluten sensitivity: An expanding paradigm

“…However, no study has so far analyzed in depth the nature of this association. The available data relies mainly on observational studies aiming to elucidate the prevalence of this condition, which ranges around the 25%[ 3 - 8 , 34 , 35 ]. However, the lack of case-control studies is a serious limitation to ascertain the reliability of the association.…”