title: An immunoepidemiological approach to asthma: identification of in-vitro T-cell response patterns associated with different wheezing phenotypes in children.
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.
  
  
  RESULTS
  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 alpha, and interferon gamma 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 gamma 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 gamma production. BHR in non-atopics was associated with elevated allergen-specific and polyclonal interleukin 10 production.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Telethon Institute for Child Health Research, Centre for Child Health Research, Faculty of Medicine and Dentistry, The University of Western Australia, Perth, Australia.
authors.forename: T
authors.initials: T
authors.lastname: Heaton
authors.forename: J
authors.initials: J
authors.lastname: Rowe
authors.forename: S
authors.initials: S
authors.lastname: Turner
authors.forename: R C
authors.initials: RC
authors.lastname: Aalberse
authors.forename: N
authors.initials: N
authors.lastname: de Klerk
authors.forename: D
authors.initials: D
authors.lastname: Suriyaarachchi
authors.forename: M
authors.initials: M
authors.lastname: Serralha
authors.forename: B J
authors.initials: BJ
authors.lastname: Holt
authors.forename: E
authors.initials: E
authors.lastname: Hollams
authors.forename: S
authors.initials: S
authors.lastname: Yerkovich
authors.forename: K
authors.initials: K
authors.lastname: Holt
authors.forename: P D
authors.initials: PD
authors.lastname: Sly
authors.forename: J
authors.initials: J
authors.lastname: Goldblatt
authors.forename: P
authors.initials: P
authors.lastname: Le Souef
authors.forename: P G
authors.initials: PG
authors.lastname: Holt
mesh_terms: D000293:Adolescent; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity; D002648:Child; D004802:Eosinophilia; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology; D007378:Interleukins / Q000378:metabolism; D010641:Phenotype; D039981:Pyroglyphidae / Q000276:immunology; D012135:Respiratory Sounds; D012882:Skin Tests; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D007378:Interleukins