House dust bioactivities predict skin prick test reactivity for children with high risk of allergy

Background: Although evidence suggests that ambient exposures to endotoxin and other immunostimulants during early life influence allergic risk, efforts to understand this host-environment relationship have been hampered by a paucity of relevant assays. Objectives: These investigations determined whether parameters of house dust extract (HDE) bioactivity were predictive of allergen skin prick test (SPT) reactivity for infants at high risk of allergy participating in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS). Methods: We conducted a nested case-control study, selecting 99 CCAAPS children who had positive SPT results to at least 1 aeroallergen at age 3 years and 101 subjects with negative SPT results. HDEs were prepared from dust samples collected from the subjects' homes at age 1 year. Murine splenocytes and bone marrow-derived dendritic cells were incubated with HDEs, and supernatant cytokine concentrations were determined by means of ELISA. Alternatively, bone marrow-derived dendritic cells were preincubated with HDEs, and then LPS-induced IL-6 responses were assessed. HDE endotoxin levels were determined by using the limulus amebocyte lysate assay. Results: HDEs derived from the homes of children with positive (cases) and negative (control subjects) SPT results had similar bioactivities. However, when cases were considered in isolation, HDEs with higher levels of bioactivity were significantly associated with children who had lower numbers of positive SPT results. Analogous statistical analyses did not identify any association between HDE endotoxin levels and the aeroallergen sensitization profiles of children included in this study. Conclusion: HDE immunostimulatory activities predicted the aeroallergen sensitization status of CCAAPS subjects better than HDE endotoxin levels. These results provide the first published evidence that HDE bioassays have clinical relevance in predicting atopic risk. (J Allergy Clin Immunol 2012;129:1529-37.)