loading page

Childhood CCL18, CXCL10 and CXCL11 levels differentially relate to and predict allergy development
  • +3
  • Johanna Huoman,
  • Sadia Haider,
  • Angela Simpson,
  • Clare Murray,
  • Adnan Custovic,
  • Maria Jenmalm
Johanna Huoman
Linköping University
Author Profile
Sadia Haider
Imperial College London
Author Profile
Angela Simpson
The University of Manchester
Author Profile
Clare Murray
The University of Manchester
Author Profile
Adnan Custovic
Imperial College London
Author Profile
Maria Jenmalm
Linköping University
Author Profile

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.

Peer review status:ACCEPTED

19 Apr 2021Submitted to Pediatric Allergy and Immunology
25 Apr 2021Reviewer(s) Assigned
17 May 2021Review(s) Completed, Editorial Evaluation Pending
18 May 2021Editorial Decision: Revise Minor
28 May 20211st Revision Received
31 May 2021Review(s) Completed, Editorial Evaluation Pending
02 Jun 2021Editorial Decision: Accept