Unraveling mechanisms of allergen sensitization and allergic rhinitis via the nasal transcriptome.

Abstract

Allergen sensitization is a critical early step in the pathogenesis of allergic disease. Different allergens likely trigger distinct immune pathways in the nasal epithelium. Our aim was to examine molecular mechanisms in the nasal epithelium for sensitization to different allergens. We recruited 301 participants and profiled their sensitization to 10 allergens and nasal epithelial transcriptome. Differential expression, gene ontology, causal network, and key driver analyses were performed to identify molecular processes underlying sensitization to indoor allergens, pollens, and pet allergens, as well as for allergic rhinitis (AR). The cohort was 48.8% female, with a mean age of 13.2 years (SD = 4.1 years). Most of the cohort was sensitized to at least 1 allergen, with 74.1% sensitized to an indoor allergen, 60.1% pollen sensitized, and 68.1% pet sensitized. In all, 51.8% of the cohort had AR. Using a discovery and test set framework for rigor, we identified and validated 185 transcripts associated with allergen sensitization. Probabilistic causal network and key driver analyses identified a network for allergen sensitization spanning 4 subnetworks for lymphocyte chemotaxis, mast cell, IL-4, and antiviral response. Although the key drivers and transcripts for indoor allergen sensitization mapped to the lymphocyte chemotaxis and antiviral response subnetworks, those for pollen sensitization mapped to the mast cell and IL-4 subnetworks. Pet sensitization mapped to lymphocyte chemotaxis, mast cell, and IL-4. The key drivers for AR significantly overlapped with those for allergen sensitization. Causal network analysis of nasal transcriptome revealed allergen-specific biologic processes and key drivers underlying sensitization and AR.