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.
Keywords: allergy, asthma, CCL18, chemokine, CXCL10, CXCL11,
sensitisation
Key messages: Chemokines are highly involved in the development
of allergic disease, by promoting recruitment to the allergic reaction
site. While previous studies have shown associations of childhood
chemokine levels with development of allergic manifestations, we were in
this study able to show longitudinal impact of chemokine levels in
infancy and childhood on the development of sensitisation and asthma
both contemporaneously as well as later in life. This suggests
chemokines as important biomarkers for allergic disease, which could
potentially be useful in a clinical setting for predicting development
of sensitisation and asthma.