西班牙各地区儿童鼻炎和哮喘中暴露组驱动的分子致敏特征

文献信息

中文摘要

背景： 儿童期过敏性鼻炎和哮喘源于遗传易感性与暴露组之间的动态相互作用。然而，环境异质性如何塑造生命早期的分子IgE致敏谱仍未被充分表征。
方法： 我们开展了一项前瞻性、观察性、多中心、横断面研究，纳入354名（0-15岁）患有过敏性鼻炎和/或哮喘的儿童，这些儿童来自八个具有不同区域气候背景的西班牙城市。所有患者对至少一种气传过敏原皮肤点刺试验呈阳性，并使用ALEX平台进行了多重组分解析诊断。分析了致敏模式，并应用无监督方法识别分子特征。
结果： 分子IgE谱分析揭示了一个结构化的致敏图景，97.5%的儿童对至少一种过敏原表现出反应性。观察到以螨虫相关的优势模式，以及部分不同的花粉相关和上皮相关模式。PCA识别出复合分子致敏梯度以及各招募中心参与者分布的描述性差异，尽管各中心之间观察到大量重叠。按年龄分层的分析识别出致敏的非线性轨迹，其特征为在高暴露环境中早期分子致敏启动，随后在学龄期IgE水平和过敏原致敏显著扩展。鼻炎严重程度与更密集的螨虫致敏网络密切相关。相比之下，哮喘严重程度并非仅由螨虫致敏驱动，而是由复杂的花粉相关多致敏驱动。
结论： 儿童IgE致敏被结构化为与地理和年龄相关的分子模式，这与环境背景在早期过敏轨迹中发挥作用相一致。

英文摘要

BACKGROUND: Allergic rhinitis and asthma in childhood arise from dynamic interactions between genetic predisposition and the exposome. However, how environmental heterogeneity shapes molecular IgE sensitization profiles during early life remains insufficiently characterized.
METHODS: We conducted a prospective, observational, multicentre, cross-sectional study including 354 children (0-15 years) with allergic rhinitis and/or asthma recruited across eight Spanish cities contrasting regional climatic contexts. All patients were skin prick test-positive to at least one aeroallergen and underwent multiplex component-resolved diagnostics using the ALEX platform. Sensitization patterns were analyzed, and unsupervised approaches were applied to identify molecular signatures.
RESULTS: Molecular IgE profiling revealed a structured sensitization landscape, with 97.5% of children exhibiting reactivity to at least one allergen. A dominant mite-related pattern and partially distinct pollen- and epithelial-related patterns were observed. PCA identified composite molecular sensitization gradients and descriptive differences in participant distributions across recruitment centres, although substantial overlap was observed between centres. Age-stratified analyses identified a non-linear trajectory of sensitization, characterized by early molecular priming in high-exposure environments, followed by a marked expansion of IgE levels and allergen sensitization during school age. Rhinitis severity was strongly associated with a denser mite sensitization network. In contrast, asthma severity was driven not by mite sensitization alone but by a complex pollen-related polysensitization.
CONCLUSION: Pediatric IgE sensitization is structured into molecular patterns associated with geography and age, consistent with a role for environmental context in early allergic trajectories.