Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo, Japan; R&D Center, NH Foods Ltd., Ibaraki, Japan.
R&D Center, NH Foods Ltd., Ibaraki, Japan.
Allergol Int. 2022 Oct;71(4):528-535. doi: 10.1016/j.alit.2022.03.006. Epub 2022 Apr 18.
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.
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.
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.
Two protease-digested EWs showed potential as optimal EW products for early introduction for primary prevention of egg allergy.
早期食物引入可诱导耐受,但经皮暴露,特别是通过湿疹损伤,可促进 IgE 致敏。为了安全有效地进行鸡蛋过敏的初级预防,我们研究了几种蛋白酶消化的蛋清(EW)产品的三个特性:1)诱导口服耐受,防止 IgE 致敏,2)弱 IgE 结合,即使在 IgE 致敏的小鼠中也能预防过敏反应,3)即使与发炎的皮肤接触,也能最小化经皮 IgE 致敏。
在最佳条件下,用几种蛋白酶消化加热的 EW。首先,给 3 周龄的 BALB/c 雌性小鼠经口给予 EW 或每种蛋白酶消化的 EW 产品,然后用氢氧化铝进行腹腔内卵清蛋白(OVA)或卵类黏蛋白(OVM)注射。测量血清 OVA 和 OVM 特异性 IgE 滴度。其次,用 OVA/OVM 致敏 6 周龄的小鼠,在腹腔内给予 EW 或每种蛋白酶消化的 EW 后测量直肠温度。第三,将 EW 或每种蛋白酶消化的 EW 产品每周 3 天应用于胶带剥离的皮肤 3 周。测量血清 OVA 和 OVM 特异性 IgE 滴度。
口服胃蛋白酶消化的 EW 产品(PDEW)和 Thermoase PC10F 消化的 EW 产品(TDEW)显著抑制 OVA/OVM 特异性 IgE 的产生。两种产品均未引起 OVA/OVM 致敏小鼠体温下降(过敏反应)。与 EW 暴露的小鼠相比,经皮暴露于 PDEW 或 TDEW 的小鼠血清 OVA/OVM 特异性 IgE 水平显著降低。
两种蛋白酶消化的 EW 作为早期引入鸡蛋过敏初级预防的最佳 EW 产品具有潜力。