A chimeric human-cat fusion protein blocks cat-induced allergy
A chimeric human-cat fusion protein blocks cat-induced allergy
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DOI：
10.1038/nm1219
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发表时间：
2005-03
期刊：
影响因子：
82.9
通讯作者：
Daocheng Zhu;C. Kepley;K. Zhang;T. Terada;Takechiyo Yamada;A. Saxon
中科院分区：
文献类型：
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作者：
Daocheng Zhu;C. Kepley;K. Zhang;T. Terada;Takechiyo Yamada;A. Saxon
动物过敏原是引起哮喘和过敏性鼻炎的重要原因。我们设计并测试了由截断的人IgG Fcγ1和猫主要过敏原Fel d1组成的嵌合人猫融合蛋白，作为过敏免疫治疗新方法的概念证明。该Fcγ-Fel d1蛋白诱导Fel d1驱动的ige介导的组胺释放剂量依赖性抑制猫过敏供者嗜碱性粒细胞和致敏的人脐带血来源肥大细胞。这种抑制与Syk和ERK信号的改变有关。在人IgE抗体对猫被动致敏的Fcγ-Fel d1转基因小鼠和对Fel d1主动致敏的Balb/c小鼠中，Fcγ-Fel d1蛋白也能阻断其体内反应活性。单独的Fcγ-Fel d1蛋白不诱导介质释放。嵌合人fc γ-变应原融合蛋白可能为变应性疾病的免疫治疗提供新的治疗平台。
Animal allergens are an important cause of asthma and allergic rhinitis. We designed and tested a chimeric human-cat fusion protein composed of a truncated human IgG Fcγ1 and the major cat allergen Fel d1, as a proof of concept for a new approach to allergy immunotherapy. This Fcγ-Fel d1 protein induced dose-dependent inhibition of Fel d1-driven IgE-mediated histamine release from cat-allergic donors' basophils and sensitized human cord blood-derived mast cells. Such inhibition was associated with altered Syk and ERK signaling. The Fcγ-Fel d1 protein also blockedin vivoreactivity in FcεRIα transgenic mice passively sensitized with human IgE antibody to cat and in Balb/c mice actively sensitized against Fel d1. The Fcγ-Fel d1 protein alone did not induce mediator release. Chimeric human Fcγ-allergen fusion proteins may provide a new therapeutic platform for the immune-based therapy of allergic disease.