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IgE唾液酸化影响过敏反应
2020-05-22 14:29

美国哈佛医学院Robert M. Anthony研究组最近取得新进展。他们发现免疫球蛋白EIgE)的唾液酸化是过敏性致病性的决定因素。2020520日出版的《自然》杂志发表了这一成果。

他们对患有花生过敏的个体和没有过敏症的非特应性个体的总IgE糖基化模式进行了无偏鉴定。他们的分析显示,与非特应性个体相比,患有花生过敏的个体的总IgE中唾液酸含量增加。

在几种变应性疾病的功能模型中,从IgE中去除唾液酸可减弱效应细胞的脱颗粒和过敏反应。治疗性干预措施(包括用针对IgE受体FcεRI的神经氨酸酶从细胞结合的IgE中除去唾液酸,并施用脱唾液酸化的IgE可明显减少过敏反应。

总之,这些结果确定了IgE糖基化,特别是唾液酸化,是过敏性疾病的重要调节剂。

据了解,世界上约有三分之一的人口患有过敏症。接触过敏原会使与肥大细胞和嗜碱性粒细胞结合的IgE抗体交联,从而触发炎症介质(包括组胺)的释放。尽管过敏绝对需要IgE,但尚不清楚为什么总的和过敏原特异性IgE浓度与过敏性疾病没有可复制的相关性。众所周知,IgG的糖基化决定了其效应功能,并具有疾病特异性模式。但是,IgE聚糖是否在疾病状态上有所不同或影响生物学活性是完全未知的。

附:英文原文

Title: Sialylation of immunoglobulin E is a determinant of allergic pathogenicity

Author: 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

Issue&Volume: 2020-05-20

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 disease3,4,5. 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.

DOI: 10.1038/s41586-020-2311-z

Source: https://www.nature.com/articles/s41586-020-2311-z

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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