Patterns of immune development in urban preschoolers with recurrent wheeze and/or atopy

Abstract

Background: Disadvantaged urban children have high rates of allergic diseases and wheezing, which are diseases associated with type 2-biased immunity.

Objective: We sought to determine whether environmental exposures in early life influence cytokine responses that affect the development of recurrent wheezing illnesses and allergic sensitization.

Methods: A birth cohort of 560 urban families was recruited from neighborhoods with high rates of poverty, and 467 (83%) children were followed until 3 years of age. Cytokine responses were measured in blood cell samples obtained at birth (cord blood) and ages 1 and 3 years. Cytokine responses were examined in relation to personal characteristics and environmental exposures to allergens and endotoxin and to the development of allergic sensitization and recurrent wheeze assessed at age 3 years.

Results: Cytokine responses generally increased with age, but responses at birth were poorly predictive for those at ages 1 and 3 years. Exposure to certain allergens (cockroach, mouse, dust mite) was significantly associated with enhanced cytokine responses at age 3 years, including IFN-α and IL-10 responses to certain stimulants and responses to phytohemagglutinin. Regarding the clinical outcomes, reduced LPS-induced IL-10 responses at birth were associated with recurrent wheeze. In contrast, reduced respiratory syncytial virus-induced IL-8 responses and increased 5'-cytosine-phosphate-guanine-3' (CpG)-induced IL-12p40 and allergen-induced IL-4 responses were associated with atopy.

Conclusions: These findings suggest that diverse biologic exposures, including allergens and endotoxin, in urban homes stimulate the development of cytokine responses in early life, and that cytokine responses to specific microbial and viral stimuli are associated with the development of allergic sensitization and recurrent wheeze.

Keywords: Cytokines; allergy; children; cord blood; immune development; mononuclear cells; wheezing.

Copyright © 2017 American Academy of Allergy, Asthma & Immunology. All rights reserved.

Figures

Figure 1

Network analysis of cytokine by stimulant data measured longitudinally. The map uses the correlation matrix among the 164 variables as the proximity matrix to create the network. More highly correlated variables are closer to each other. Correlations greater than 0.26 (95th percentile) in absolute value are represented with lines. The age at which the cytokine responses were assessed is color coded.

Figure 2

Associations between season of birth and cytokine responses at year 3. The graphs depict significant associations (p

Figure 3

Association between bedroom dust allergens at years 1 through 3 and cytokine responses to innate (A) and adaptive (B) stimuli at year 3. Colored squares depict positive (blue) and negative (red) Pearson correlations. Associations significant at the 0.05 level are marked with an asterisk; significant associations after correction for multiple comparisons are outlined. Blank spaces represent responses that were generally below the level of detection.

Figure 4

Association between cytokine responses at each year and outcomes at year 3. Colored squares depict positive (blue) and negative (red) odds ratios. Associations significant at the 0.05 level are marked with an asterisk; significant associations after correction for multiple comparisons are outlined. Blank spaces represent responses that were generally below the level of detection, or were not measured.