Analysis of glutathione S-transferase allergen cross-reactivity in a North American population: Relevance for molecular diagnosis
Analysis of glutathione S-transferase allergen cross-reactivity in a North American population: Relevance for molecular diagnosis
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DOI：
10.1016/j.jaci.2015.03.015
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发表时间：
2015-11-01
影响因子：
14.2
通讯作者：
Pomes, Anna
中科院分区：
文献类型：
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作者：
Mueller, Geoffrey A.;Pedersen, Lars C.;Pomes, Anna
背景资料：目前尚不清楚是否交叉反应或共致敏谷胱甘肽S-转移酶（GST）发生在热带和亚热带环境。在美国，Bla g 5是最重要的GST过敏原，缺乏与某些物种GST的共暴露可以更好地评估交叉反应性。目的：目的：研究蟑螂（Bla g 5）、尘螨（Dust mites）、鸡胚（Cervix（Der p 8 and Blo t 8），and helminth（Asc s 13）对于潜在的交叉反应位点，和评估的IgE交叉反应性的致敏患者从温带气候这些过敏原的分子诊断purposes.Methods：四个晶体结构进行了测定。对蟑螂和螨过敏的患者血清进行了IgE反应性测试，这些GST。一组6鼠抗Bla g 5单克隆抗体进行了评估与其他3 GST使用抗体结合assays.Results的交叉反应性：过敏原结构的比较，形成2-域单体，二聚化，揭示了一些类似的暴露残基的连续区域，呈现交叉反应性不太可能。因此，来自北美患者的抗Bla g 5或抗Der p 8 IgE分别不识别Der p 8或Bla g 5，也不显示与Blo t 8或Asc s 13的结合。通过抑制测定观察到抗Bla g 5 IgE与Der p 8的结合比Bla g 5弱（类似于100倍），类似于抗Bla g 5 mAb对Der p 8的弱识别。来自热带哥伦比亚的患者有IgE的所有4 GSTs.Conclusions：缺乏显着的IgE交叉反应之间的4 GST是在协议的低共享氨基酸的身份在分子表面。每个GST是需要在不同的地理区域进行准确的分子诊断。
Background: It is not clear whether cross-reactivity or cosensitization to glutathione S-transferases (GSTs) occurs in tropical and subtropical environments. In the United States, Bla g 5 is the most important GST allergen and lack of coexposure to GSTs from certain species allows a better assessment of cross-reactivity.Objectives: To examine the molecular structure of GST allergens from cockroach (Bla g 5), dust mites (Der p 8 and Blo t 8), and helminth (Asc s 13) for potential cross-reactive sites, and to assess the IgE cross-reactivity of sensitized patients from a temperate climate for these allergens for molecular diagnostic purposes.Methods: Four crystal structures were determined. Sera from patients allergic to cockroach and mite were tested for IgE reactivity to these GSTs. A panel of 6 murine anti-Bla g 5 mAb was assessed for cross-reactivity with the other 3 GSTs using antibody binding assays.Results: Comparisons of the allergen structures, formed by 2-domain monomers that dimerize, revealed few contiguous regions of similar exposed residues, rendering cross-reactivity unlikely. Accordingly, anti-Bla g 5 or anti-Der p 8 IgE from North American patients did not recognize Der p 8 or Bla g 5, respectively, and neither showed binding to Blo t 8 or Asc s 13. A weaker binding of anti-Bla g 5 IgE to Der p 8 versus Bla g 5 (similar to 100-fold) was observed by inhibition assays, similar to a weak recognition of Der p 8 by anti-Bla g 5 mAb. Patients from tropical Colombia had IgE to all 4 GSTs.Conclusions: The lack of significant IgE cross-reactivity among the 4 GSTs is in agreement with the low shared amino acid identity at the molecular surface. Each GST is needed for accurate molecular diagnosis in different geographic areas.