Predicting asthma phenotypes: characterization of IL1RL1 in asthma

Not being able to breathe, wheezing, coughing, feeling like you are suffocating…This is what happens during an asthma attack, which affects about 100,000 children in the Netherlands. Asthma is caused by a complex interaction between genetic and environmental factors. An important asthma gene is interleukin-1 receptor–like 1 (IL1RL1), which is expressed a.o. on inflammatory cells in the lungs. The gene encodes different proteins: IL1RL1-a and IL1RL1-b. Binding of the cytokine IL-33 to IL1RL1-b leads to an inflammatory response and, in contrast, binding of IL-33 to IL1RL1-a is thought to inhibit an inflammatory response.This study shows that the IL33-IL1RL1 pathway is associated with wheezing, especially after the age of 2 till 4 years old, and that it plays an important role in the development of childhood onset (eosinophilic, allergic) asthma. There are many gene variants that pose a risk of asthma. These variants may or may not encode a protein. A novel finding is that mostly non-coding gene variants are important regulators for IL1RL1 and the amount of IL1RL1 protein. In addition, we report that IL1RL1 variants that constitute a risk for asthma influence asthma treatment response in asthmatic children and that the amount of IL1RL1-a levels present in blood can be used to predict eosinophilic asthma at the age of 6 years. Finally, we show that genetic variants have no added value in predicting asthma at birth.The results of this study highly advanced our understanding of the (epi)genetic effects of IL1RL1 in relation to asthma. This contributes to better prediction of asthma and the development of new treatment options for specific asthma phenotypes