More fuel to the fire: Some patients with non-celiac gluten sensitivity exhibit adaptive immunological responses in duodenal mucosa

Abstract Background In contrast to the well characterized Celiac Disease (CD), the clinical scenarios encompassed in non-celiac gluten sensitivity (NCGS) might be related to different antigens that trigger distinct immune-inflammatory reactions. Although an increased number of intestinal intraepithelial lymphocytes is observed at the inception of both diseases, subsequent immunopathogenic pathways seems to be different. Aims To compare the immunological profile in the duodenal mucosa of patients with CD, self-reported gluten intolerant subjects and gluten tolerant patients with functional dyspepsia (GT-FD). Methods In a blind, cross-sectional study, duodenal biopsies from 15 consecutive untreated patients with active CD, 9 NCGS individuals and 10 GT-FD subjects were studied by flow-cytometry and immunohistochemistry. We determined the presence of pro-inflammatory cytokine expressing monocytes and monocyte-derived dendritic cells involved in innate immune activation, cytokine-driven polarization and maintenance of Th1 and Th17/Th22, and anti-inflammatory/profibrogenic cytokines. Results CD patients presented a higher percentage of cells expressing all tested cytokines in lamina propria and epithelium than GT-FD group. Cytokines that induce and maintain Th1 and Th17 polarization were higher in CD compared to NCGS and GT-FD cases; and higher in NCGS compared to GT-FD. Similar differences in the expression of IL-4 and TGF- β1 were detected, while IL-10-expressing cells were lower in NCGS patients compared to CD and GT-FD subjects. Conclusions NCGS patients exhibit components of both, innate and adaptive immune mechanisms but to a lesser extent compared to CD. The clinical characteristics and HLA status of our NCGS group resemble that described in subjects with irritable bowel syndrome sensible to gluten and probably represents a distinct phenotype of this syndrome.