Allergen-Specific IL-5 Responses in Early Childhood Predict Asthma at Age Eight

<div><p>Background</p><p>The pattern of development of allergen-specific T cell cytokine responses in early childhood and their relation to later disease is poorly understood. Here we describe longitudinal changes in allergen-stimulated T cell cytokine responses and their relation to asthma and allergic disease during the first 8 years of life.</p><p>Methods</p><p>Subjects with a family history of asthma, who were enrolled antenatally in the Childhood Asthma Prevention Study (public trials registration number ACTRN12605000042640), had skin prick tests, clinical evaluation for asthma and eczema, and <i>in vitro</i> assessment of T cell cytokine responses to HDM extract performed at ages 18 months (n = 281), 3 years (n = 349), 5 years (n = 370) and 8 years (n = 275). We measured interleukin (IL-) 13 at 3, 5 and 8 years, and IL-5, IL-10, and interferon-γ (IFN-γ), at 18 months, 3, 5 and 8 years by ELISA. A cohort analysis was undertaken. Independent effects of cytokine responses at each age on the risk of asthma and allergic outcomes at age 8 years were estimated by multivariable logistic regression.</p><p>Results</p><p>HDM-specific IL-5 responses increased with age. HDM-specific IL-13 and IL-10 responses peaked at age 5 years. HDM-specific IL-5 responses at 3 years, 5 years and 8 years were significantly associated with the presence of asthma and atopy at 8 years. IL-13 responses at 3 years, 5 years and 8 years were significantly associated with atopy at 8 years, but this association was not independent of the effect of IL-5. Other HDM-specific cytokine responses were not independently related to asthma or eczema at 8 years.</p><p>Conclusion</p><p>HDM-specific IL-5 responses at age 3 years or later are the best measure of T cell function for predicting asthma at age 8 years.</p></div

Relative risk of HDM-specific cytokine response and presence of atopy, asthma and eczema.

<p>The relative risk of HDM-specific IL-5, IL-13 and IL-10 responses at each time point and the presence of atopy (a), asthma (b) and eczema (c). Relative risks for low responders (10–50 pg/mL) and high responders (>50 pg/mL) compared with non-responders (<10 pg/mL) are shown with 95% CIs. Relative risks are not adjusted for other cytokines measured at the same age. n.a. = non applicable.</p

Flowchart for Childhood Asthma Prevention Study (followed to age 8 years).

<p>The size of the cohort at each assessment (18 months, 3 years, 5 years, 8 years): number of participants, number of blood samples, number of valid cytokine responses.</p

HDM-specific cytokine responses in asthmatic and non-asthmatic children.

<p>Box and whisker plots showing the distribution of HDM-specific IL-5, IL-13, IL-10 and IFN-γ cytokine responses at 18 months, 3, 5 and 8 years in asthmatic and non-asthmatic children at 8 years.</p

Characteristics of the study population at different ages.

<p>Characteristics of the study population at different ages.</p

HDM-specific cytokine responses in atopic and non-atopic children.

<p>Box and whisker plots showing the distribution of HDM-specific IL-5, IL-13, IL-10 and IFN-γ cytokine responses at 18 months, 3, 5 and 8 years in atopic and non-atopic children at 8 years.</p

The frequency (n) of HDM-specific cytokine T-cell responses at age 8 years.

<p>n: number of subjects.</p