Protease-digested egg-white products induce oral tolerance in mice but elicit little IgE production upon epicutaneous exposure

Abstract

Background: Early food introduction induces tolerance, but epicutaneous exposure, especially via eczema lesions, promotes IgE sensitization. Aiming for safe and effective primary prevention of egg allergy, we examined several protease-digested egg-white (EW) products for three properties: 1) induction of oral tolerance that prevents IgE sensitization, 2) weak IgE binding that can prevent allergic reactions even in IgE-sensitized mice, and 3) minimal epicutaneous IgE sensitization even when in contact with inflamed skin. Methods: Heated EW was digested with several proteases under optimal conditions. First, three-week-old BALB/c female mice were intragastrically administered EW or each protease-digested EW product, followed by intraperitoneal ovalbumin (OVA) or ovomucoid (OVM) injection with alum. Serum OVA- and OVM-specific IgE titers were measured. Second, six-week-old mice were sensitized with OVA/OVM, and the rectal temperature was measured after intraperitoneal administration of EW or each protease-digested EW. Third, EW or each protease-digested EW product was applied to the tape-stripped skin for 3 days/week for 3 weeks. Serum OVA- and OVM-specific IgE titers were measured. Results: Orally administered pepsin-digested EW product (PDEW) and Thermoase PC10F-digested EW product (TDEW) significantly suppressed OVA-/OVM-specific IgE production. Neither product elicited a body temperature decline (anaphylaxis) in OVA-/OVM-sensitized mice. Serum OVA-/OVM-specific IgE levels were significantly lower in mice epicutaneously exposed to PDEW or TDEW than in EW-exposed mice. Conclusions: Two protease-digested EWs showed potential as optimal EW products for early introduction for primary prevention of egg allergy.

Keywords

• Enzyme digestion
• Epicutaneous sensitization
• Food allergy
• Oral tolerance
• Primary prevention