Wheat gliadin deamidated by cation-exchange resins induces oral tolerance in a mouse model of wheat allergy (1)
The currently understood mechanism of the oral-SIT is thought to be associated with the modification of cellular and humoral response to allergens. The provocation of possi-
bly life-threatening anaphylactic reaction occasionally occurs with this therapy, due to the multivalent B-cell epitopes crosslinked with IgE present on the surface of mast cells and basophils. Gliadin and glutenin, the major proteins of wheat, are the principal allergens of wheat-dependent exercise-induced anaphylaxis (WDEIA). Gliadin has many similar IgE binding epitopes with the sequences of the glutamine residues tandem. Undeamidated gliadin (UG) and Deamidated gliadin (DG) were used for sensitization of mice.
The intestinal permeability of HRP at 60 min after incubation was enhanced in the UG and Control groups. The histamine level was enhanced in UG-treated and untreated mice.
The level of gliadin-specific IgE in the sera was significantly enhanced in the Control and UG groups, whereas the enhancement of IgE production was significantly suppressed in the DG group. The IgG1 level of the DG group was significantly lower than that of the UG and Control groups, whereas the IgG2a and IgA level of the DG group was significantly higher than that of the UG and Control groups.
The level of IL-4 cytokine (Th2 cytokine) of the DG group was significantly lower than that of the UG and Control groups.
Wheat-dependent exercise-induced anaphylaxis (WDEIA) is caused by an IgE response after the intake of a wheat allergen and physical exercise. Wheat ω-5 gliadin is a major allergen in WDEIA. ω-5 gliadin constitute the primary structure of IgE-binding epitopes such as QQIPQQQ, QQSPQQQ, and QQFPQQQ. Allergic inflammation in the small intestine enhances intestinal permeability leading to the considerable rise in the serum allergen level after its administration because of probable absorption of large molecules of antigen protein from the small intestine. IL-4 induces the production of allergen-specific IgE and IgG1 and inhibits the production of Th1 cytokines like interferon-γ (IFN-γ). Repeated oral administration of DG induced oral tolerance by producing Treg cells and suppressing Th2-immune responses.
Oral administration of 2 or 20 mg peanut protein followed by its immunization (100 μg) did not induce tolerance, but that of 100 mg peanut protein successfully induced oral tolerance.