Relationship between cytokine expression patterns and clinical outcomes: Two population-based birth cohorts

Wu, J., Prosperi, M. C. F., Simpson, A., Hollams, E. M., Sly, P. D., Custovic, A. and Holt, P. G. (2015) Relationship between cytokine expression patterns and clinical outcomes: Two population-based birth cohorts. Clinical and Experimental Allergy, 45 12: 1801-1811. doi:10.1111/cea.12579

Author Wu, J.
Prosperi, M. C. F.
Simpson, A.
Hollams, E. M.
Sly, P. D.
Custovic, A.
Holt, P. G.
Title Relationship between cytokine expression patterns and clinical outcomes: Two population-based birth cohorts
Journal name Clinical and Experimental Allergy   Check publisher's open access policy
ISSN 1365-2222
Publication date 2015-12-01
Year available 2015
Sub-type Article (original research)
DOI 10.1111/cea.12579
Open Access Status DOI
Volume 45
Issue 12
Start page 1801
End page 1811
Total pages 11
Place of publication West Sussex, United Kingdom
Publisher Wiley-Blackwell Publishing
Language eng
Formatted abstract

Models that incorporate patterns of multiple cytokine responses to allergens, rather than individual cytokine production, may better predict sensitization and asthma.


To characterize the patterns of peripheral blood mononuclear cells’ (PBMCs) cytokine responses to house dust mite (HDM) allergens among children from two population-based birth cohorts using machine learning techniques.


PBMCs collected at 8 years of age from the UK Manchester Asthma and Allergy Study (n = 268) and at 14 years of age from the Australian Raine Study (n = 1374) were cultured with HDM extract (10 μg/ml). Cytokine expression (IL-13, IL-5, IFN-γ, and IL10) was measured in the supernatant. Cytokine patterns were identified using a Gaussian mixture model clustering, and classification stability was assessed by bootstrapping.


A six-class model indicated complex latent structure of cytokine expression. Based on the characteristics of each class, we designated them as follows: ‘Nonresponders’ (n = 905, 55%); ‘IL-10 responders’ (n = 49, 3%); ‘IFN-γ and IL-13 medium responders’ (n = 56, 3.4%); ‘IL-13 medium responders’ (n = 351, 21.4%); ‘IL-5 and IL-13 medium responders’ (n = 77, 4.7%); and ‘IL-13 and IL-5 high responders’ (n = 204, 12.4%). ‘IL-13 and IL-5 high responders’ were at much higher risk of HDM sensitization and asthma compared to all other classes, with 88% of children assigned to this class being sensitized and 28.5% having asthma.


Using model-based clustering, we identified several distinct patterns of cytokine response to HDM and observed interplay between cytokine expression level, cytokine patterns (especially IL-13 and IL-5), and clinical outcomes. ‘IL-13 and IL-5 high responders’ class was strongly associated with HDM sensitization. However, among HDM-sensitized children, one-third showed no PBMC response to HDM, and the majority of HDM-sensitized children did not have asthma or wheeze. Our findings suggest that positive HDM ‘allergy tests’ and asthma are associated with a broad range of immunophenotypes, which may have important implications for the use of cytokine-targeted treatment approaches.
Keyword Asthma
Cytokine pattern
House dust mite allergens
Raine Study
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
Child Health Research Centre Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 3 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 3 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 20 Dec 2015, 10:24:31 EST by System User on behalf of Scholarly Communication and Digitisation Service