Functional and clinical translation of asthma and allergy associated genetic variants in IL33 and IL1RL1

In this thesis we aimed to unravel novel mechanisms underlying asthma and allergy, and to translate this to clinical application. The focus is on 2 genes: Interleukin 33 (IL33) and Interleukin-1-Receptor-Like-1 (IL1RL1). These encode the protein IL-33, an alarm substance in inflammation and the target protein it binds to: IL-1RL1. We describe the distinct genetic signals in IL33 and IL1RL1 that specifically associate with an eosinophilic subtype of asthma and with severe asthma characterized by low lung function. Eosinophilic asthma is asthma with high levels of eosinophilic immune cells. Also these genetic signals in IL33 and IL1RL1 linked to function of lung cells and immune cells, for example these associated with the levels of IL-33 and IL-1RL1, with less viability and increased immune response of these cells. We show that genotype and levels of this pathway could contribute to the prediction of specific asthma and allergy phenotypes. Therefore, this thesis concludes that genetic variation and levels could have potential as biomarker in the prediction of disease, as well as targeted drugs directed at the IL-33/IL-1RL1 pathway may be useful drugs in specific patient groups of asthma and allergy.