Circulating Chemokine Levels and the Development of Allergic Phenotypes from Infancy to Adolescence: A Population-Based Birth Cohort Study

Abstract Background: Chemokines are important mediators in immune cell recruitment, contributing to allergy development. However, extensive studies of chemokines in the circulation in relation to the presence and development of allergic diseases remain scarce.Objective: To investigate associations of circulating allergy-related chemokines with development of asthma and sensitisation cross-sectionally and longitudinally in a population-based cohort. Methods: The chemokines CCL17, CCL22, CXCL10, CXCL11 and CCL18 were measured in plasma samples from children in a population-based birth cohort. Samples were available from cord blood at birth (n=376) and age 1 (n=195) and 8 years (n=334). Cross-sectional and longitudinal association analyses were performed in relation to asthma and allergic sensitisation, as well as allergic phenotype clusters previously derived using machine learning in the same study population.Results: In children with asthma and/or allergic sensitisation, CCL18 levels at ages 1 and/or 8 were consistently elevated. In a longitudinal model which included information on asthma from 4 time-points (ages 5, 8, 11 and 16 years), we observed a significant association between increasing levels of CCL18 at age 1 year and a higher risk of asthma from early school age to adolescence (OR=2.9, 95% CI 1.1-7.6, p=0.028). We observed similar associations in longitudinal models for allergic sensitisation. Asthma later in life was preceded by increased CXCL10 levels after birth, and decreased CXCL11 levels at birth. Conclusion: Elevated CCL18 levels throughout childhood foreshadow the development of asthma and allergic sensitisation. The Th1-associated chemokines CXCL10 and CXCL11 were also associated with development of both outcomes, with differential temporal effects.