Phosphorylation of buckwheat allergenic proteins reduces their allergenic potential and improves therapeutic strategy

Food allergies have become a major global health concern, and their current standard treatment relies on strict avoidance of the involved allergen. Allergen-specific immunotherapy (AIT) is a effective treatment for reducing allergic symptoms through the repeated administration of increasing doses of allergens. The major disadvantage of AIT is that the administration of allergens can cause adverse side effects, including anaphylactic reactions. The use of hypoallergens is a promising alternative approach. Chemical modification techniques, including glycation and phosphorylation are efficient approaches for reducing the IgE-binding abilities of food allergens.

Buckwheat (Fagopyrum esculentum) is frequently consumed in Asian countries, and Fag e 1 and Fag e 2 are the major allergens. Dot blot analysis using serum from food-allergic patients demonstrated that the phosphorylated antigens (P-Fag e 1 and P-Fag e 2) exhibited reduced allergenicity. Mice subjected to oral administration of P-Fag e 1 or P-Fag e 2 for six weeks showed decreased serum IgE and histamine levels and increased serum IgA level after Fag e 1 or Fag e 2 sensitization, respectively, compared to the controls. Moreover, the Peyer’s patches of phosphorylated antigen-fed mice showed decreased IL-4 production and induction of T follicular helper (Tfh) cells. Fag e 2 is highly resistant to proteolysis; however, the peptic digestibility of Fag e 2 was enhanced by phosphorylation. The orally administered peptic hydrolysate of P-Fag e 2 attenuated IgE-mediated allergic reactions via enhanced IgA levels in Fag e 2-sensitized mice. These results suggest P-Fag e 2 is easily digested in the stomach and induces the attenuation of IgE-mediated allergic reactions.