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 and 140 school-age and 131 preschool children with asthma/wheeze from the Unbiased BIOmarkers for the PREDiction of respiratory diseases outcomes cohort, of whom 595 had severe disease. We applied clustering methods to identify 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 with 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 among school children and adults with allergic asthma.

中文翻译：

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多种变应原特异性IgE抗体之间的连通性模式及其与严重哮喘的关系。

背景

过敏性致敏与严重哮喘有关，但大多数指南不建议对致敏性进行评估。

目的

我们假设在轻度/中度哮喘和重度哮喘的致敏参与者之间，IgE对多种变应原性蛋白质的反应模式有所不同。

方法

使用多重阵列测量了来自无偏性生物标志物的509名成人，140名学龄儿童和131名学龄前哮喘/喘息儿童的IgE对呼吸道疾病结局队列的预测，使用112例过敏性分子（组分，c-sIgE）进行了IgE检测。严重的疾病。我们应用聚类方法来识别组件的共现模式（组件群集）和参与者之间的敏化模式（敏化群集）。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严重和轻度/中度哮喘之间c-sIgE相互作用的差异。

结果

确定了四个致敏簇，但疾病严重程度组之间没有差异。同样，成分簇与哮喘的严重程度无关。没有发现c-sIgE与严重哮喘有关。与严重哮喘相比，轻度/中度学龄儿童与成人之间的主要区别在于c-sIgE之间的联系网络。患有严重哮喘的参与者之间的连接性较高，但这些连接性较弱。中度/中度网络的连接较少，但连接更牢固。没有结构同源性的组件之间的连通性倾向于在患有严重哮喘的参与者中同时发生。结果独立于轻度/中度和重度组的不同样本量。

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患有过敏性哮喘的成年人中哮喘严重程度的预测指标。