An immunoepidemiological approach to asthma: identification of in-vitro T cell response patterns associated with different wheezing phenotypes in children

HeatonT, RoweJ, TurnerS, AalberseRC, deKlerkN, SuriyaarachchiD, MSerralhaM, HoltBJ, HollamsE, YerkovichS, HoltK, Sly, P. D., GoldblatJ, LeSouefP and HoltPG (2005) An immunoepidemiological approach to asthma: identification of in-vitro T cell response patterns associated with different wheezing phenotypes in children. Lancet, 365 9454: 142-149. doi:10.1016/S0140-6736(05)17704-6


Author HeatonT
RoweJ
TurnerS
AalberseRC
deKlerkN
SuriyaarachchiD
MSerralhaM
HoltBJ
HollamsE
YerkovichS
HoltK
Sly, P. D.
GoldblatJ
LeSouefP
HoltPG
Title An immunoepidemiological approach to asthma: identification of in-vitro T cell response patterns associated with different wheezing phenotypes in children
Journal name Lancet   Check publisher's open access policy
ISSN 0140-6736
Publication date 2005-01-01
Year available 2005
Sub-type Article (original research)
DOI 10.1016/S0140-6736(05)17704-6
Open Access Status DOI
Volume 365
Issue 9454
Start page 142
End page 149
Total pages 8
Place of publication London
Publisher Lancet Publishing Group British ed
Language eng
Subject 110701 Allergy
Abstract Background Increasing evidence suggests that patterns of T cell immunity to inhalant allergens in genetically diverse human populations are more heterogeneous than previously assumed, and that covert differences in expression patterns might underlie variations in airway disease phenotypes. We tested this proposition in a community sample of children Methods We analysed data from 172 individuals who had been recruited antenatally to a longitudinal birth cohort study. Of the 194 birth cohort participants, data from the 147 probands (age range 8·6–13·5 years) who consented to blood collection were included along with data from 25 consenting siblings (mean age 11 years [range 7·4–17·4]). We ascertained clinical phenotypes related to asthma and allergy. We measured T cell responses to allergens and mitogens, together with blood eosinophils and IgE/IgG antibodies, and assessed associations between these indices and clinical phenotypes. Findings Atopy was associated with allergen-specific T-helper (Th)2 responses dominated by interleukin 4, interleukin 5, interleukin 9, interleukin 13, whereas interleukin 10, tumour necrosis factor α, and interferon γ responses were common to both atopics and non atopics. The wheal size from skin prick with allergen was positively associated with in-vitro interleukin 5 and interferon γ responses, and negatively associated with interleukin 10. Asthma, especially in atopics, was strongly associated with eosinophilia/interleukin 5, and bronchial hyper-responsiveness (BHR) was associated with eosinophilia plus polyclonal interferon γ production. BHR in non-atopics was associated with elevated allergen-specific and polyclonal interleukin 10 production. Interpretation Parallel immunological and clinical profiling of children identified distinctive immune response patterns related to asthma and wheeze compared with BHR, in atopics non-atopics. Immunological hyper-responsiveness, including within the Th1 cytokine compartment, is identified as a hallmark of BHR. Relevance to practice These findings highlight the heterogeneity of immune response patterns in asthmatic children, including those with seemingly homogeneous Th2-driven atopic asthma. Further elucidation of the covert relationships between wheezing phenotypes and underlying immunophenotypes in this age group will potentially lead to more effective treatments for what is an unexpectedly heterogeneous collection of disease subtypes.
Keyword Medicine
Q-Index Code C1
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
 
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Created: Fri, 27 Mar 2009, 22:17:59 EST by Ms Karen Naughton on behalf of School of Medicine