Faculty Opinions recommendation of Redefining the intraepithelial lymphocytes threshold to diagnose gluten sensitivity in patients with architecturally normal duodenal histology.

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.

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

10.21203/rs.3.rs-32731/v1 ◽

2020 ◽

Author(s):

Antonia Isabel Castillo-Rodal ◽

Janette Furuzawa-Carballeda ◽

Mario Pelaez-Luna ◽

Jose Castro-Gomez ◽

Yolanda Lopez-Vidal ◽

...

Keyword(s):

Duodenal Mucosa ◽

Cross Sectional Study ◽

Intraepithelial Lymphocytes ◽

Gluten Sensitivity ◽

Cross Sectional ◽

Inflammatory Reactions ◽

Immunological Responses ◽

Clinical Scenarios ◽

Irritable Bowel ◽

Tgf Β1

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.

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