Exposome-driven molecular sensitization signatures in pediatric rhinitis and asthma across Spanish regions.

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.