IL1RL1 Gene Variants and Nasopharyngeal IL1RL-a Levels Are Associated with Severe RSV Bronchiolitis: A Multicenter Cohort Study

Targets for intervention are required for respiratory syncytial virus (RSV) bronchiolitis, a common disease during infancy for which no effective treatment exists. Clinical and genetic studies indicate that IL1RL1 plays an important role in the development and exacerbations of asthma. Human IL1RL1 encodes three isoforms, including soluble IL1RL1-a, that can influence IL33 signalling by modifying inflammatory responses to epithelial damage. We hypothesized that IL1RL1 gene variants and soluble IL1RL1-a are associated with severe RSV bronchiolitis.We studied the association between RSV and 3 selected IL1RL1 single-nucleotide polymorphisms rs1921622, rs11685480 or rs1420101 in 81 ventilated and 384 non-ventilated children under 1 year of age hospitalized with primary RSV bronchiolitis in comparison to 930 healthy controls. Severe RSV infection was defined by need for mechanical ventilation. Furthermore, we examined soluble IL1RL1-a concentration in nasopharyngeal aspirates from children hospitalized with primary RSV bronchiolitis. An association between SNP rs1921622 and disease severity was found at the allele and genotype level (p = 0.011 and p = 0.040, respectively). In hospitalized non-ventilated patients, RSV bronchiolitis was not associated with IL1RL1 genotypes. Median concentrations of soluble IL1RL1-a in nasopharyngeal aspirates were >20-fold higher in ventilated infants when compared to non-ventilated infants with RSV (median [and quartiles] 9,357 [936-15,528] pg/ml vs. 405 [112-1,193] pg/ml respectively; p<0.001).We found a genetic link between rs1921622 IL1RL1 polymorphism and disease severity in RSV bronchiolitis. The potential biological role of IL1RL1 in the pathogenesis of severe RSV bronchiolitis was further supported by high local concentrations of IL1RL1 in children with most severe disease. We speculate that IL1RL1a modifies epithelial damage mediated inflammatory responses during RSV bronchiolitis and thus may serve as a novel target for intervention to control disease severity

Predictive value of soluble urokinase plasminogen activator receptor, soluble ST2, and IL-33 in bronchopulmonary dysplasia

BACKGROUND: Bronchopulmonary dysplasia (BPD) remains an important complication of preterm births. The soluble form of ST2 (sST2), interleukin-33 (IL-33), and soluble form of the urokinase plasminogen activator receptor (suPAR) have attracted increasing attention as biomarkers for different diseases. The aim of the current study was to assess the predictive value of plasma sST2, IL-33, and suPAR levels in patients with risk of BPD development