Department of Pediatric Allergy and Immunology, Duke University Medical Center, Durham, NC 27710, USA.
J Allergy Clin Immunol. 2012 Sep;130(3):716-23. doi: 10.1016/j.jaci.2012.05.044. Epub 2012 Jul 11.
IgE-mediated allergic reactions to cashews and other nuts can trigger life-threatening anaphylaxis. Proactive therapies to decrease reaction severity do not exist.
We aimed to determine the efficacy of pepsin-digested cashew proteins used as immunotherapy in a murine model of cashew allergy.
Mice 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.
Pepsinized 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: T(H)2-type cytokine secretion from splenocytes was decreased, whereas specific IgG(1) and IgG(2a) levels were increased.
Pepsinized cashew proteins are effective in treating cashew allergy in mice and appear to work through the same mechanisms as native protein immunotherapy.
IgE 介导的腰果和其他坚果过敏反应可引发危及生命的过敏反应。目前尚无预防过敏反应严重程度的主动治疗方法。
我们旨在确定作为免疫疗法的胃蛋白酶消化腰果蛋白在腰果过敏的小鼠模型中的疗效。
将小鼠致敏于腰果，然后用消化或天然腰果过敏原进行挑战，以评估蛋白制剂的变应原性。使用天然或胃蛋白酶化腰果蛋白，小鼠进行口服或腹腔内致敏方案，以确定蛋白制剂的免疫原性。最后，对腰果致敏的小鼠进行天然或胃蛋白酶化腰果蛋白的免疫治疗方案，并随后进行激发挑战。
胃蛋白酶化腰果蛋白引起的过敏反应弱于天然腰果蛋白，但重要的是保留了刺激细胞增殖和细胞因子产生的能力。用胃蛋白酶化蛋白致敏的小鼠在挑战用天然过敏原时会发生反应，这表明胃蛋白酶化过敏原在体内仍具有免疫原性。与安慰剂相比，用胃蛋白酶化腰果过敏原进行免疫治疗后，在挑战天然和胃蛋白酶化蛋白时，过敏症状和体温下降明显减少。用天然或胃蛋白酶化过敏原进行免疫治疗后的免疫变化相似：脾细胞分泌的 T(H)2 型细胞因子减少，而特异性 IgG(1)和 IgG(2a)水平增加。
胃蛋白酶化腰果蛋白在治疗小鼠腰果过敏方面有效，并且似乎通过与天然蛋白免疫疗法相同的机制起作用。
