Serological, genomic and structural analyses of the major mite allergen Der p 23.
Serological, genomic and structural analyses of the major mite allergen Der p 23.
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主要螨过敏原p23的血清学，基因组和结构分析。
DOI：
10.1111/cea.12680
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发表时间：
2016-02
期刊：
影响因子：
--
通讯作者：
Pomés A
中科院分区：
文献类型：
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作者：
Mueller GA;Randall TA;Glesner J;Pedersen LC;Perera L;Edwards LL;DeRose EF;Chapman MD;London RE;Pomés A
Der p 23最近在欧洲人群中被鉴定为主要过敏原和潜在的几丁质结合蛋白。本研究旨在评估Der p 23在北美人群中其他尘螨变应原中的重要性，并确定其结构以进行功能表征。通过ELISA测量IgE与Der p 23、Der p 1、Der p 2、Der p 5、Der p 7和Der p 8的结合。RNA-seq数据来自D.比较屋尘螨作为过敏原表达水平的估计值。通过X射线晶体学和NMR分析了结构。尽管Der p 23的患病率很高（Der p 1和Der p 2分别为75%对87%和79%），但抗Der p 23 IgE水平相对较低。患者对测试的6种过敏原的反应是可变的（n=47），但平均抗Der p 1和抗Der p 2一起占特异性IgE的85%。就丰度而言，Der p 23的RNA表达水平是主要过敏原中最低的，比Der p 2低30倍和7倍。Der p 23的结构是由两个二硫键稳定的小球状蛋白，其在结构上与含有结合几丁质的碳水化合物结合结构域的过敏原如Blo t 12相关。功能测定未能证实几丁质结合Der p 23。Der p 23占对螨变应原的IgE应答的一小部分，其由Der p 1和Der p 2主导。Der p 23和Der p 2的特异性IgE的流行率和量与其他尘螨变应原的表达相比不成比例地高。
Der p 23 was recently identified in a European population as a major allergen and potentially a chitin binding protein. This study sought to assess the importance of Der p 23 among other Dermatophagoides allergens in a North American population, and to determine the structure for functional characterization. IgE binding to Der p 23, Der p 1, Der p 2, Der p 5, Der p 7, and Der p 8 was measured by ELISA. RNA-seq data from D. pteronyssinus were compared as estimates of allergen expression levels. The structure was analyzed by X-ray crystallography and NMR. Despite a high prevalence of Der p 23, (75% versus 87% and 79% for Der p 1 and Der p 2, respectively), the anti-Der p 23 IgE levels were relatively low. The patient response to the 6 allergens tested was variable (n=47), but on average anti-Der p 1 and anti-Der p 2 together accounted for 85% of the specific IgE. In terms of abundance, the RNA expression level of Der p 23 is the lowest of the major allergens, 30-fold less than and 7-fold less than Der p 2. The structure of Der p 23 is a small, globular protein stabilized by two disulfide bonds, which is structurally related to allergens such as Blo t 12 that contain carbohydrate binding domains that bind chitin. Functional assays failed to confirm chitin binding by Der p 23. Der p 23 accounts for a small percentage of the IgE response to mite allergens, which is dominated by Der p 1 and Der p 2. The prevalence and amount of specific IgE to Der p 23 and Der p 2 are disproportionately high compared to the expressions of other Dermatophagoides allergens.