Predictors of interleukin-33 and thymic stromal lymphopoietin levels in cord blood
- DOI
- Language of the publication
- English
- Date
- 2015-02-18
- Type
- Article
- Author(s)
- Ashley-Martin, Jillian
- Dodds, Linda
- Arbuckle, Tye E.
- Levy, Adrian R.
- Platt, Robert W.
- Marshall, Jean S.
- Publisher
- Wiley
Abstract
Background: The fetal immune system is a critical window of development. The epithelial cell-derived cytokines, thymic stromal lymphopoietin (TSLP), and interleukin-33 (IL-33) have received attention for their role in allergic responses but not been studied during this critical window. The objectives were to assess correlations among IL-33, TSLP, and IgE in umbilical cord blood samples and identify prenatal predictors of these biomarkers. Methods: This study utilized data and banked cord blood collected in the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a trans-Canada cohort study of 2001 pregnant women. Our analytic sample comprised the 1254 women with a singleton, term birth with a cord blood sample. Spearman correlation coefficients (SCC) and logistic regression models were used to examine associations between biomarkers and identify potential predictors of elevated biomarker levels. Results: Thymic stromal lymphopoietin and IL-33 were more strongly correlated with each other (SCC = 0.75, p < 0.0001) than with IgE (IL-33 SCC = 0.14, TSLP SCC = 0.21). Maternal allergy, heavy street traffic, and elevated birth weight were significantly associated with jointly elevated TSLP and IL-33 levels, whereas maternal age and female infant sex were inversely associated with elevated IgE. Conclusions: In this population of Canadian women and infants, TSLP and IL-33 were detectable in cord blood, more strongly correlated with each other than with IgE, and associated with maternal characteristics indicative of inflammatory responses. This study motivates investigation into the value of cord blood IL-33 and TSLP levels as childhood allergy predictors and raises interesting questions regarding in utero coordinated regulation of these cytokines.
Plain language summary
Childhood asthma and allergies are a significant public health problem affecting Canadians and a better understanding of the underlying disease processes is needed to devise strategies to better manage these conditions. Early-life detection of childhood allergies, asthma, and atopic dermatitis may minimize the burden of these childhood diseases by facilitating early intervention strategies. Previous efforts at early-life detection have focused on measuring levels of Immunoglobulin E (IgE) in umbilical cord blood. While IgE is elevated in allergic responses, cord blood measurements of IgE have been shown to be a poor predictor of childhood allergies, asthma, and atopic dermatitis. The involvement of two cytokines, Thymic Stromal Lymphopoietin (TSLP) and Interleukin-33 (IL-33), has recently been observed in animal studies but has not been studied in newborns. The objectives of this study were 1) to determine whether umbilical cord blood levels of IgE, TSLP and IL-33 are correlated with each other and 2) to identify prenatal predictors of these biomarkers. Data and biospecimens were analysed from the Maternal-Infant Research on Environmental Chemicals (MIREC) Biobank, a trans-Canada cohort study of 2001 pregnant women. TSLP and IL-33 were found to be highly correlated with each other but less correlated with IgE. Maternal allergy, self-reported exposure to heavy street traffic, and birth weight were statistically significantly associated with elevated levels of both TSLP and IL-33. Maternal age and female sex were inversely associated with elevated levels of IgE. These findings provide supporting human evidence for the toxicological hypothesis that both TSLP and IL-33 play a critical role in the immunological pathways that lead to development of childhood allergic diseases. This study provides motivation for further investigation into the ability of cord blood TSLP and IL-33 levels to predict future childhood asthma, allergies and atopic dermatitis. This work was led by researchers at Dalhousie University. Health Canada co-developed the MIREC Study and assisted with interpretation of results for this work.
Subject
- Health,
- Health and safety