Th104 - The human colon as the source of IgE and the role of microbiota in food-sensitized patients

Abstract Text: Food allergies are provoked by an aberrant immunological reaction to food components. Evidences of IgE production in the human gut and IgE memory cells are scarce. We found that colorectal polyps from children with rectal bleeding and sensitized to food allergens are dominated by an inflammatory cell infiltration. We aimed to study immunoregulatory mechanisms and IgE synthesis in polyps.
Polyps were removed and adjacent biopsies were grabbed. We found that 44% of patients had pedunculated colorectal polyps, 83% showed the presence of IgE, and the stroma had a dense infiltration of eosinophils and mononuclear cells. Our findings showed a significantly higher frequency of IgE+CD138+ cells (B cells) and IgE+CD138- (eosinophils) within polyps than in the adjacent tissue. Germinal centers with proliferation, hypermutation and class-switch of B cells, along with markers for IgE switching, and IgE+ memory B cells (CD45+CD19+CD138+CD27+IgD-IgE+ cells) were detected in 85.7% of polyps analyzed. The polyp stroma showed a type-2 inflammatory environment, with high levels of IL-4 IL-5, IL-33 and TSLP and a high IL-13/IFN-γ ratio compared to the surrounding tissue, and the presence of milk-specific IL-13-producing T cells expressing CCR9, concurrent with CCL25 polyp expression. Finally, the whole microbiota and that attached to the polyp tissue was similar to that described in food- allergic patients with a lower frequency of Firmicutes and enhanced Bacteroidetes.
In conclusion, we found that IgE is produced in polyps with IgE+ B cell memory, likely influenced by the strong type-2 inflammation and microbiota associated with food allergy.