An immunoepidemiological approach to asthma: identification of in vitro T-cell response patterns associated with different wheezing phenotypes amongst 11 year olds

T. Heaton, J. Rowe, Stephen William Turner, R. C. Aalberse, N. de Klerk, D. Suriyaachichi, M. Serralha, B. Holt, J. Goldblatt, P. N. Le Souef, P. D. Sly, P. G. Holt

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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 a, 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 hyperresponsiveness (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.

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 hyperresponsiveness, 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.

Original languageEnglish
Pages (from-to)142-149
Number of pages7
JournalThe Lancet
Volume365
DOIs
Publication statusPublished - 2005

Keywords

  • AIRWAY HYPERRESPONSIVENESS
  • BRONCHIAL RESPONSIVENESS
  • RESPIRATORY SYMPTOMS
  • ATOPIC-DERMATITIS
  • IMMUNE-RESPONSE
  • 2 POPULATIONS
  • ALLERGEN
  • TH1
  • INTERLEUKIN-10
  • EOSINOPHILS

Cite this

An immunoepidemiological approach to asthma: identification of in vitro T-cell response patterns associated with different wheezing phenotypes amongst 11 year olds. / Heaton, T.; Rowe, J.; Turner, Stephen William; Aalberse, R. C.; de Klerk, N.; Suriyaachichi, D.; Serralha, M.; Holt, B.; Goldblatt, J.; Le Souef, P. N.; Sly, P. D.; Holt, P. G.

In: The Lancet, Vol. 365, 2005, p. 142-149.

Research output: Contribution to journalArticle

Heaton, T, Rowe, J, Turner, SW, Aalberse, RC, de Klerk, N, Suriyaachichi, D, Serralha, M, Holt, B, Goldblatt, J, Le Souef, PN, Sly, PD & Holt, PG 2005, 'An immunoepidemiological approach to asthma: identification of in vitro T-cell response patterns associated with different wheezing phenotypes amongst 11 year olds', The Lancet, vol. 365, pp. 142-149. https://doi.org/10.1016/S0140-6736(05)17704-6
Heaton, T. ; Rowe, J. ; Turner, Stephen William ; Aalberse, R. C. ; de Klerk, N. ; Suriyaachichi, D. ; Serralha, M. ; Holt, B. ; Goldblatt, J. ; Le Souef, P. N. ; Sly, P. D. ; Holt, P. G. / An immunoepidemiological approach to asthma: identification of in vitro T-cell response patterns associated with different wheezing phenotypes amongst 11 year olds. In: The Lancet. 2005 ; Vol. 365. pp. 142-149.
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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 childrenMethods 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 a, 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 hyperresponsiveness (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.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 hyperresponsiveness, 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.",
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T1 - An immunoepidemiological approach to asthma: identification of in vitro T-cell response patterns associated with different wheezing phenotypes amongst 11 year olds

AU - Heaton, T.

AU - Rowe, J.

AU - Turner, Stephen William

AU - Aalberse, R. C.

AU - de Klerk, N.

AU - Suriyaachichi, D.

AU - Serralha, M.

AU - Holt, B.

AU - Goldblatt, J.

AU - Le Souef, P. N.

AU - Sly, P. D.

AU - Holt, P. G.

PY - 2005

Y1 - 2005

N2 - 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 childrenMethods 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 a, 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 hyperresponsiveness (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.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 hyperresponsiveness, 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.

AB - 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 childrenMethods 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 a, 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 hyperresponsiveness (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.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 hyperresponsiveness, 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.

KW - AIRWAY HYPERRESPONSIVENESS

KW - BRONCHIAL RESPONSIVENESS

KW - RESPIRATORY SYMPTOMS

KW - ATOPIC-DERMATITIS

KW - IMMUNE-RESPONSE

KW - 2 POPULATIONS

KW - ALLERGEN

KW - TH1

KW - INTERLEUKIN-10

KW - EOSINOPHILS

U2 - 10.1016/S0140-6736(05)17704-6

DO - 10.1016/S0140-6736(05)17704-6

M3 - Article

VL - 365

SP - 142

EP - 149

JO - The Lancet

JF - The Lancet

SN - 0140-6736

ER -