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

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Title: Relationship between cytokine expression patterns and clinical outcomes: two population-based birth cohorts
Authors: Wu, J
Prosperi, MC
Simpson, A
Hollams, EM
Sly, PD
Custovic, A
Holt, PG
Item Type: Journal Article
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.
Issue Date: 19-Nov-2015
Date of Acceptance: 25-Apr-2015
ISSN: 1365-2222
Publisher: Wiley
Start Page: 1801
End Page: 1811
Journal / Book Title: Clinical and Experimental Allergy
Volume: 45
Issue: 12
Copyright Statement: © 2015 The Authors. Clinical & Experimental Allergy. Published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: MAAS
Raine Study
Cytokine pattern
House dust mite allergens
Public Health And Health Services
Publication Status: Published
Conference Place: England
Appears in Collections:Department of Medicine
Faculty of Medicine

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