Etiology of Pediatric Atopy

Henry Ford Health System, Detroit MI

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Abstract

DESCRIPTION (provided by applicant): Our objective is to study the relationship of early-life cat and dog exposure to potential persistent effects on T-cell cytokine profiles, biologic markers of atopy, and clinical atopy among a well-characterized birth cohort (n=835), the Detroit area Childhood Allergy Study (CAS), as they reach 18 years of age. Extensive early-life environmental exposure data have been collected on this cohort. Outcomes will include total IgE, allergen-specific IgE and IgG4 levels, intracellular IL-4, IL-10 and interferon (IFN)gamma in mitogen stimulated T-cells and current or history of allergic rhinitis and asthma. Hypotheses: Compared to subjects with low levels of exposure, those with high-level exposure to dogs and cats in the first year of life will exhibit: i) a persistently altered immune response at age 17, typified by a low IL-4/IFN-gamma ratio and elevated IL- 10 secretion in response to T-cell mitogenic stimulation; ii) reduced levels of allergenspecific IgE and increased allergen-specific IgG4 to common aeroallergens; and, iii) a persistently reduced risk for allergic rhinitis and asthma. The specific aims include analyzing the number of indoor pets during the first year of life, adjusting for well-established confounders and effect modifiers, for persistent effects on: i) T-cell intracellular cytokine levels of IL-4, IFN-gamma and IL-10; ii) serum levels of allergen-specific IgE (cat, dog, dust mite, ragweed, grass and alternaria) and allergen-specific IgG4 (cat, dog, grass and dust mite); iii) current and lifetime history of self-reported and doctor diagnosed allergic rhinitis and asthma. We will also iv) study the relationship between these outcomes and v) evaluate the role of biomarkers and history of atopy in each parent in the above analyses. Methods: The CAS cohort will be followed-up by questionnaire and a home visit at age 18 years. Stimulated T cell cytokine analysis, total IgE and serum allergen-specific IgE and IgG4 levels will be determined and cohort subjects and parents will answer a questionnaire regarding subject and parental history of symptoms and diagnosis of allergic rhinitis and asthma and post early life pet exposure. Blood specimens, DNA and mRNA from parents and subjects will be placed in a biorepository for future molecular epidemiology studies.