Childhood CCL18, CXCL10 and CXCL11 levels differentially relate to and
predict allergy development
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. Our aim was 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 the Manchester Asthma and Allergy Study. Samples were
available from cord blood at birth (n=376), 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 were consistently elevated at ages
1 and/or 8 years. In a longitudinal model including information on
asthma from 4 time-points (ages 5, 8, 11 and 16 years), we observed a
significant association between increasing CCL18 levels at age 1 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 precede
the development of asthma and allergic sensitisation. The Th1-associated
chemokines CXCL10 and CXCL11 also associated with development of both
outcomes, with differential temporal effects.