Pepsinized cashew proteins are hypoallergenic and immunogenic and provide effective immunotherapy in mice with cashew allergy

BackgroundIgE-mediated allergic reactions to cashews and other nuts can trigger life-threatening anaphylaxis. Proactive therapies to decrease reaction severity do not exist.ObjectivesWe aimed to determine the efficacy of pepsin-digested cashew proteins used as immunotherapy in a murine model of cashew allergy.MethodsMice were sensitized to cashew and then underwent challenges with digested or native cashew allergens to assess the allergenicity of the protein preparations. Using native or pepsinized cashew proteins, mice underwent oral or intraperitoneal sensitization protocols to determine the immunogenic properties of the protein preparations. Finally, cashew-sensitized mice underwent an immunotherapy protocol with native or pepsinized cashew proteins and subsequent provocation challenges.ResultsPepsinized cashew proteins elicited weaker allergic reactions than native cashew proteins but importantly retained the ability to stimulate cellular proliferation and cytokine production. Mice sensitized with pepsinized proteins reacted on challenge with native allergens, demonstrating that pepsinized allergens retain immunogenicity in vivo. Immunotherapy with pepsinized cashew allergens significantly decreased allergic symptoms and body temperature decrease relative to placebo after challenge with native and pepsinized proteins. Immunologic changes were comparable after immunotherapy with native or pepsinized allergens: TH2-type cytokine secretion from splenocytes was decreased, whereas specific IgG1 and IgG2a levels were increased.ConclusionsPepsinized cashew proteins are effective in treating cashew allergy in mice and appear to work through the same mechanisms as native protein immunotherapy.