Mechanisms of asthma and allergic inflammation
IL-5 T-cell responses to house dust mite are associated with the development of allergen-specific IgE responses and asthma in the first 5 years of life

https://doi.org/10.1016/j.jaci.2007.06.034Get rights and content

Background

Allergen-specific TH2-like cytokine responses are considered to be important in sensitization and allergic diseases.

Objective

To examine the profile of house dust mite (HDM) stimulated T-cell cytokines and their relationship to allergic disease in children over the period of the first 5 years of life.

Methods

Subjects with a family history of asthma who were enrolled antenatally in the Childhood Asthma Prevention Study and had skin prick tests, clinical evaluation for asthma and eczema, and in vitro assessment of lymphocyte cytokine responses to HDM extract performed at ages 18 months (n = 281), 3 years (n = 349), and 5 years (n = 370). IL-13 at 3 and 5 years and IL-5, IL-10, and IFN- γ at 18 months, 3 years, and 5 years were measured by ELISA.

Results

House dust mite–specific cytokine responses increased with age for all cytokines except IFN-γ. HDM-specific IL-5 responses at 3 years and 5 years were significantly positively related to skin prick test positivity at 5 years. IL-5 responses at 5 years were also significantly related to asthma at 5 years. Other HDM-specific cytokine responses were not related to asthma or eczema at 5 years. Responses were not altered by a HDM avoidance intervention.

Conclusion

IL-5 responses to HDM, the dominant local inhalant allergen, are related to the expression of clinical illness at age 5 years.

Clinical implications

The T-cell response to HDM, as reflected in IL-5 production, is acquired over the first years of life and may play a role in the expression of allergic airways disease.

Section snippets

Methods

The study was conducted in Sydney, Australia, a region where HDM is the dominant local allergen.13 Pregnant women whose unborn children were at high risk of developing asthma were recruited from the antenatal clinics in Sydney, Australia. Subjects (n = 616) were randomized to active and control arms for both HDM avoidance and the dietary intervention, separately, by using a factorial design. The trial objectives and design, including details of the participants, interventions, and environmental

Characteristics of the population

Valid data for 1 or more cytokine responses were available for 485 subjects, of whom 244 (50.3%) were male subjects and 242 (49.9%) had been randomly allocated to the active HDM avoidance group. There were 281 subjects with valid data for 1 or more cytokines at 18 months, 349 at 3 years, and 370 at 5 years (see this article's Table E1 in the Online Repository at www.jacionline.org). The proportion of subjects with positive SPTs to any allergen increased with age, and the proportion of these who

Discussion

House dust mite–specific IL-5 responses at ages 3 and 5 years were associated with allergic sensitization at 5 years, and IL-5 responses at 5 years were associated with asthma at that age. IL-5 responses were not related to the presence of eczema at this age. In contrast IL-13, IL-10, and IFN- γ responses to HDM were not independently related to asthma, eczema, or sensitization at age 5 years. HDM-specific IL-5, IL-13, and IL-10 increased over the first 5 years of life. HDM-specific IFN-γ

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    Supported by National Health and Medical Research Council of Australia; the Cooperative Research Center for Asthma; the New South Wales Department of Health; the Children's Hospital Westmead; the Swiss National Science Foundation, PBZHB-114742 (C.W.-C.); the Swedish Heart Lung Foundation; and the Swedish Society of Medicine (C.A.). Contributions of goods and services were made by Allergopharma Joachim Ganzer KG Germany, John Sands Australia, Hasbro, Toll Refrigerated, AstraZeneca Australia, and Nu-Mega Ingredients Pty Ltd. Goods were provided at reduced cost by Auspharm, Allersearch, and Meadow Lea Foods.

    Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.

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