多种过敏原特异性IgE抗体之间的连通性及其与重症哮喘的关系
2020/04/07
摘要
背景：变应性致敏与重症哮喘有关，但大多数指南不建议对致敏性进行评估。
目的：我们假设，患有轻/中症哮喘或重症哮喘的致敏受试者对多种变应原性蛋白质的IgE应答模式不同。
方法：研究人群来自U-BIOPRED队列，包括患有哮喘或有喘鸣的509名成年人，140名学龄儿童和131名学龄前儿童，其中595名重症哮喘患者，在该群体中使用多重阵列检测了112种变应原性分子的IgE（组分，c-sIgE）。我们应用聚类方法来识别和共现组分模式（组分簇）和受试者致敏模式（致敏簇）。网络分析技术探索了c-sIgE的连通性结构，而差分网络分析则寻找了重症和轻/中症哮喘之间c-sIgE相互作用的差异。
结果：研究确定了四个致敏簇，但疾病不同严重程度组之间没有差异。同样组分簇与哮喘的严重程度也无关。没有发现c-sIgE与重症哮喘相关。与重症哮喘相比，轻/中症的学龄儿童患者与成人患者之间的主要区别在于c-sIgE之间的联系网络。重症哮喘受试者组分致敏连通性较高，但这些连通性较弱。轻/中症哮喘的连通性较少，但连通性更强。没有结构同源性的组分之间的连通性倾向于在患有重症哮喘的受试者中同时发生。结果独立于轻/中症组和重症组。
结论：IgE与多种变应原蛋白之间的相互作用模式是学龄儿童和成年过敏性哮喘患者哮喘严重程度的预测指标。
Connectivity patterns between multiple allergen specific IgE antibodies and their association with severe asthma.
Roberts G, Fontanella S, Selby A, Howard R, Filippi S, Hedlin G, Nordlund B, Howarth P, Hashimoto S, Brinkman P, Fleming LJ, Murray C, Bush A, Frey U, Singer F, Malby Schoos AM, van Aalderen W, Djukanovic R, Chung KF, Sterk PJ, Custovic A; U-BIOPRED Consortium.
Abstract
BACKGROUND:Allergic sensitization is associated with severe asthma, but assessment of sensitization is not recommended by most guidelines.
OBJECTIVE:We hypothesized that patterns of IgE responses to multiple allergenic proteins differ between sensitized participants with mild/moderate and severe asthma.
METHODS:IgE to 112 allergenic molecules (components, c-sIgE) was measured using multiplex array among 509 adults, 140 school-age and 131 pre-school children with asthma/wheeze from U-BIOPRED cohort, of whom 595 had severe disease. We applied clustering methods to identify and co-occurrence patterns of components (component clusters) and patterns of sensitization among participants (sensitization clusters). Network analysis techniques explored the connectivity structure of c-sIgE, and differential network analysis looked for differences in c-sIgE interactions between severe and mild/moderate asthma.
RESULTS:Four sensitization clusters were identified, but with no difference between disease severity groups. Similarly, component clusters were not associated with asthma severity. None of the c-sIgE were identified as associates of severe asthma. The key difference between school-children and adults with mild/moderate compared to those with severe asthma was in the network of connections between c-sIgE. Participants with severe asthma had higher connectivity among components, but these connections were weaker. The mild/moderate network had fewer connections, but the connections were stronger. Connectivity between components with no structural homology tended to co-occur among participants with severe asthma. Results were independent from the different sample sizes of mild/moderate and severe groups.
CONCLUSIONS:The patterns of interactions between IgE to multiple allergenic proteins are predictors of asthma severity amongst school-children and adults with allergic asthma.
背景：变应性致敏与重症哮喘有关，但大多数指南不建议对致敏性进行评估。
目的：我们假设，患有轻/中症哮喘或重症哮喘的致敏受试者对多种变应原性蛋白质的IgE应答模式不同。
方法：研究人群来自U-BIOPRED队列，包括患有哮喘或有喘鸣的509名成年人，140名学龄儿童和131名学龄前儿童，其中595名重症哮喘患者，在该群体中使用多重阵列检测了112种变应原性分子的IgE（组分，c-sIgE）。我们应用聚类方法来识别和共现组分模式（组分簇）和受试者致敏模式（致敏簇）。网络分析技术探索了c-sIgE的连通性结构，而差分网络分析则寻找了重症和轻/中症哮喘之间c-sIgE相互作用的差异。
结果：研究确定了四个致敏簇，但疾病不同严重程度组之间没有差异。同样组分簇与哮喘的严重程度也无关。没有发现c-sIgE与重症哮喘相关。与重症哮喘相比，轻/中症的学龄儿童患者与成人患者之间的主要区别在于c-sIgE之间的联系网络。重症哮喘受试者组分致敏连通性较高，但这些连通性较弱。轻/中症哮喘的连通性较少，但连通性更强。没有结构同源性的组分之间的连通性倾向于在患有重症哮喘的受试者中同时发生。结果独立于轻/中症组和重症组。
结论：IgE与多种变应原蛋白之间的相互作用模式是学龄儿童和成年过敏性哮喘患者哮喘严重程度的预测指标。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(J Allergy Clin Immunol. 2020 Mar 15. pii: S0091-6749(20)30341-9. doi: 10.1016/j.jaci.2020.02.031.)
(J Allergy Clin Immunol. 2020 Mar 15. pii: S0091-6749(20)30341-9. doi: 10.1016/j.jaci.2020.02.031.)
Connectivity patterns between multiple allergen specific IgE antibodies and their association with severe asthma.
Roberts G, Fontanella S, Selby A, Howard R, Filippi S, Hedlin G, Nordlund B, Howarth P, Hashimoto S, Brinkman P, Fleming LJ, Murray C, Bush A, Frey U, Singer F, Malby Schoos AM, van Aalderen W, Djukanovic R, Chung KF, Sterk PJ, Custovic A; U-BIOPRED Consortium.
Abstract
BACKGROUND:Allergic sensitization is associated with severe asthma, but assessment of sensitization is not recommended by most guidelines.
OBJECTIVE:We hypothesized that patterns of IgE responses to multiple allergenic proteins differ between sensitized participants with mild/moderate and severe asthma.
METHODS:IgE to 112 allergenic molecules (components, c-sIgE) was measured using multiplex array among 509 adults, 140 school-age and 131 pre-school children with asthma/wheeze from U-BIOPRED cohort, of whom 595 had severe disease. We applied clustering methods to identify and co-occurrence patterns of components (component clusters) and patterns of sensitization among participants (sensitization clusters). Network analysis techniques explored the connectivity structure of c-sIgE, and differential network analysis looked for differences in c-sIgE interactions between severe and mild/moderate asthma.
RESULTS:Four sensitization clusters were identified, but with no difference between disease severity groups. Similarly, component clusters were not associated with asthma severity. None of the c-sIgE were identified as associates of severe asthma. The key difference between school-children and adults with mild/moderate compared to those with severe asthma was in the network of connections between c-sIgE. Participants with severe asthma had higher connectivity among components, but these connections were weaker. The mild/moderate network had fewer connections, but the connections were stronger. Connectivity between components with no structural homology tended to co-occur among participants with severe asthma. Results were independent from the different sample sizes of mild/moderate and severe groups.
CONCLUSIONS:The patterns of interactions between IgE to multiple allergenic proteins are predictors of asthma severity amongst school-children and adults with allergic asthma.
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减少抗生素使用、肠道微生物群和儿童哮喘发病率的关系：基于人群和前瞻性队列研究的证据
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蛋白S通过调节Th1/Th2平衡来预防过敏性支气管哮喘
