Longitudinal trajectories of allergen sensitization in children with different transcriptome profiles from COCOA study

Allergen sensitization trajectories are linked to diverse allergic disease phenotypes, but the underlying mechanisms remain unclear. The study used skin prick test data obtained from children in the COCOA birth cohort (n = 549) at 3, 7, and 9 years of age. Sensitization to 13 aeroallergens, categorized into four groups (house dust mite [HDM], pollens, pets, and mold), was assessed and classified into trajectories using group-based multi-trajectory modeling. Blood transcriptome and cytokine analyses at age 7 were also performed. Four allergen sensitization trajectories were identified: “no sensitization” (42.8 %), “HDM only” (29.9 %), “pollen predominant” (6.0 %), and “multiple sensitization” (21.3 %). The “HDM only” and “pollen predominant” trajectories were associated with an increased risk of allergic rhinitis (AR) and allergic conjunctivitis. “Multiple sensitization” was associated with an increased risk of food allergy, atopic dermatitis, AR, and asthma during the first 9 years-of-age. IL-2 and IL-5 levels were elevated significantly in the “multiple sensitization” trajectory. Transcriptome analysis revealed that the “HDM only” trajectory was associated with B cell receptor responses, the “pollen predominant” trajectory was associated with MHC and T cell responses, and the “multiple sensitization” trajectory was associated with pathways related to barrier function, including IL-1 and tight junctions, while also sharing signaling pathways with both the “HDM only” and “pollen predominant” trajectories. Four aeroallergen sensitization trajectories with distinct transcriptome profile during childhood were detected. “Multiple sensitization” trajectory is associated with an increased risk of allergic comorbidities, potentially mediated through barrier dysfunction.