Blockade of peanut allergy with a novel Ara h 2-Fcγ fusion protein in mice
Blockade of peanut allergy with a novel Ara h 2-Fcγ fusion protein in mice
复制标题
DOI：
10.1016/j.jaci.2012.10.018
复制
发表时间：
2013-01-01
影响因子：
14.2
通讯作者：
Zhu, Daocheng
中科院分区：
文献类型：
--
作者：
Liu, Yu;Sun, Yongtao;Zhu, Daocheng
背景资料：由于过敏反应的高风险，不推荐使用花生粗提取物进行花生过敏的常规免疫疗法。过敏原特异性免疫治疗目前没有进行花生allergy.Objectives：本研究的目的是开发一种新的花生-人融合蛋白，以阻止花生诱导的allergyshocking.Methods：我们的基因设计和表达一种新的植物-人融合蛋白组成的主要花生过敏原Ara h 2和人IgG Fc γ 1。我们在纯化的人嗜碱性粒细胞中检测了Ara h 2-Fc γ融合蛋白（AHG 2）的功能。转基因小鼠表达人Fc γ RI α和小鼠花生过敏modelsused.Results：AHG 2抑制组胺释放诱导的花生过敏患者的嗜碱性粒细胞的全花生提取物（WPE），而融合蛋白本身不诱导介质释放。AHG 2抑制hFc β RI α转基因小鼠中MPE诱导的花生特异性IgE介导的被动皮肤过敏反应。AHG 2还显著抑制急性过敏反应，包括用粗花生提取物激发的WPE致敏小鼠的典型体温下降。气道的组织学评估显示，AHG 2减少了花生诱导的炎症，而融合蛋白本身并不诱导花生致敏小鼠的气道炎症。结论：AHG 2在体内外均能抑制花生特异性IgE介导的过敏反应。将特异性花生过敏原与Fc γ结合，可为花生过敏的过敏原免疫治疗提供新的途径。（J Allergy Clin Immunol 2013;131：213-21.）
Background: Conventional immunotherapy for peanut allergy using crude peanut extracts is not recommended because of the unacceptably high risk of anaphylaxis. Allergen-specific immunotherapy is not currently undertaken for peanut allergy.Objectives: The objective of this study was to develop a novel peanut-human fusion protein to block peanut-induced anaphylaxis.Methods: We genetically designed and expressed a novel plant-human fusion protein composed of the major peanut allergen Ara h 2 and human IgG Fc gamma 1. We tested the Ara h 2-Fc gamma fusion protein (AHG2)'s function in purified human basophils. Transgenic mice expressing human Fc epsilon RI alpha and a murine peanut allergy model were used.Results: AHG2 inhibited histamine release induced by whole peanut extract (WPE) from basophils of patients with peanut allergy, whereas the fusion protein itself did not induce mediator release. AHG2 inhibited the WPE-induced, peanut-specific, IgE-mediated passive cutaneous anaphylaxis in hFc epsilon RI alpha transgenic mice. AHG2 also significantly inhibited acute anaphylactic reactivity, including the prototypical decrease in body temperature in WPE-sensitized mice challenged with crude peanut extract. Histologic evaluation of the airways showed that AHG2 decreased peanut-induced inflammation, whereas the fusion protein itself did not induce airway inflammation in peanut-sensitized mice. AHG2 did not exert an inhibitory effect in mice lacking Fc gamma RII.Conclusion: AHG2 inhibited peanut-specific IgE-mediated allergic reactions in vitro and in vivo. Linking specific peanut allergen to Fc gamma can provide a new approach for the allergen immunotherapy of peanut allergy. (J Allergy Clin Immunol 2013;131:213-21.)