中国哮喘联盟

免疫球蛋白E的唾液酸化是过敏反应致病性的决定因素

2020/06/11

   摘要
   世界上大约有三分之一的人口患有过敏症。接触过敏原会与肥大细胞和嗜碱性细胞结合的免疫球蛋白E (IgE)抗体交联,从而触发包括组胺在内的炎症介质的释放。虽然IgE对于过敏反应是绝对必需的,但是为什么总IgE浓度和过敏原特异性IgE浓度与变态反应性疾病之间没有重复相关性,这一点还不清楚。众所周知,IgG的糖基化决定了其效应功能,并具有疾病特异性的模式。然而,IgE聚糖在疾病状态或影响生物活性方面是否存在差异还完全不清楚。在这里,我们对花生过敏症患者和无过敏症的非特应性人群的总IgE的糖基化模式进行了公正的检查。我们的分析显示花生过敏个体与非特应性个体相比,总IgE的唾液酸含量增加。从IgE中去除唾液酸可减弱多种变态反应性疾病模型的效应细胞脱颗粒和过敏反应。治疗包括用针对IgE受体FcεRI的神经氨酸酶从细胞结合的IgE中去除唾液酸,和给予无唾液酸的IgE明显减少过敏反应。综上所述,这些结果证实IgE糖基化,特别是唾液酸化,是过敏性疾病的重要调节因子。

 
 (中日友好医院呼吸与危重症医学科 张清 摘译 林江涛 审校 )
(Nature, 2020, doi:10.1038/s41586-020-2311-z.)


 
 
 
Sialylation of immunoglobulin E is a determinant of allergic pathogenicit
 
 Kai-Ting C. Shade, Michelle E. Conroy, Nathaniel Washburn, Maya Kitaoka, Daniel J. Huynh, Emma Laprise, Sarita U. Patil, Wayne G. Shreffler & Robert M. Anthony
 
Abstract
Approximately one-third of the world’s population suffers from allergies1. Exposure to allergens crosslinks immunoglobulin E (IgE) antibodies that are bound to mast cells and basophils, triggering the release of inflammatory mediators, including histamine2. Although IgE is absolutely required for allergies, it is not understood why total and allergen-specific IgE concentrations do not reproducibly correlate with allergic disease3–5. It is well-established that glycosylation of IgG dictates its effector function and has disease-specific patterns. However, whether IgE glycans differ in disease states or affect biological activity is completely unknown6. Here we perform an unbiased examination of glycosylation patterns of total IgE from individuals with a peanut allergy and from non-atopic individuals without allergies. Our analysis reveals an increase in sialic acid content on total IgE from individuals with a peanut allergy compared with non-atopic individuals. Removal of sialic acid from IgE attenuates effector-cell degranulation and anaphylaxis in several functional models of allergic disease. Therapeutic interventions—including removing sialic acid from cell-bound IgE with a neuraminidase enzyme targeted towards the IgE receptor FcεRI, and administering asialylated IgE—markedly reduce anaphylaxis. Together, these results establish IgE glycosylation, and specifically sialylation, as an important regulator of allergic disease.




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