3/ Minor groups of children are characterized by distinct patterns, with sensitization to pan-allergens
Our cluster analysis found that some preschool and school-age children showed multiple sensitization, including sensitization to pan-allergens. Two small clusters were characterized by sensitization to PR-10 proteins, a super-family of highly conserved pan-allergens, previously shown to be associated with asthma and allergic rhinitis at school-age (13,14,16,17). In particular, Bet v 1 was identified to be one of the five allergen molecules associated with a high risk of asthma and/or rhinitis at 16 years of age in two North European birth cohorts (18). More broadly, studies conducted in birch-free areas have suggested that sensitization to PR-10 proteins is associated with clinical phenotypes and sensitization to other allergens (19,20). Our study confirms these observations by identifying one of the PR-10 clusters in preschool recurrent wheezers, suggesting that children developing early sensitization to these pan-allergens may constitute a distinct endotype. These results also complement the findings from the network analysis of component sensitization among children from the U-BIOPRED cohort, showing that patients with SA had more frequent connections between components than those with milder disease (10).