原标题:螨虫主要过敏原Der p 23的血清学、基因组学和结构分析
——来自浙大迪迅
①最近在欧洲人群中发现Der p23是主要过敏原和潜在的甲壳素结合蛋白。②本研究旨在评估Der p23在北美人群中的重要性,以及确定功能性特征的结构。③用ELISA法检测IgE与Der p23、Der p1、Der p2、Der p5、Der p7、Der p8的结合情况。螨虫RNA-seq数据被比作是过敏原表达水平的估计。用x射线晶体学和核磁共振对其结构进行了分析。尽管Der p23的致敏率较高(达到75%、Der p 1 和 Der p 2分别为87%和79%),但抗Der p23 IgE水平相对较低。④患者对6种过敏原的反应是可变的(n = 47),但平均抗der p1和抗der p2占特异性IgE的85%。在丰度方面,Der p23的RNA表达水平是主要过敏原中最低的,比Der p1低30倍,比Der p2低7倍。Der p23的结构是一个小的球状蛋白,由两个二硫化物键稳定,结构上与Blo t12等过敏原相关,这些过敏原含有与甲壳素结合的碳水化合物结合域。功能性实验未能证实甲壳素与Der p23结合。⑤IgE对螨虫变应原的应答主要由Der p1和Der p2引起的,Der p23只占其中很小的比例。与其他尘螨过敏原的表达相比,Der p23和Der p2的致敏率和特异性IgE的数量是异常高的。
延伸阅读
Clinical & Experimental Allergy
[IF:6.5]
Serological, genomic and structural analyses of the major mite allergen Der p 23.
doi: 10.1111/cea.12680
Background
Der p 23 was recently identified in a European population as a major allergen and potentially a chitin binding protein.
Objective
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.
Methods
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 analysed by X-ray crystallography and NMR.
Results
Despite a high prevalence of Der p 23, (75% vs. 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, thirty fold less than Der p 1 and sevenfold less than Der p 2. The structure of Der p 23 is a small, globular protein stabilized by two disulphide 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.
Conclusions and Clinical Relevance
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 expression of other Dermatophagoides allergens.
All Authors:
G A. Mueller1 , T. A. Randall2 , J. Glesner3 , L. C. Pedersen1 , L. Perera1 , L. L. Edwards1 , E. F. DeRose1 , M. D. Chapman3 , R. E. London1 and A. Pomes3 1 Genome Integrity and Structural Biology Laboratory, Research Triangle Park, NC, USA, 2 Integrative Bioinformatics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA and 3 INDOOR Biotechnologies, Inc., Charlottesville, VA, USA
2018-11-10 Article
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