Etiology of Pediatric Atopy

描述（由申请人提供）：我们的目标是在底特律地区儿童过敏研究（CAS）中，在一个特征明确的出生队列（n=835）中，研究早期猫和狗暴露于对t细胞细胞因子谱、特应性生物标志物和临床特应性的潜在持续影响的关系，当它们达到18岁时。在这个队列中收集了大量的早期环境暴露数据。结果将包括总IgE，过敏原特异性IgE和IgG4水平，细胞内IL-4， IL-10和干扰素(IFN) γ在丝裂原刺激的t细胞和当前或历史过敏性鼻炎和哮喘。假设：与低水平暴露的受试者相比，那些在出生后一年内高水平暴露于狗和猫的受试者将表现出：i) 17岁时持续改变的免疫反应，典型表现为低IL-4/ ifn - γ比率和IL- 10分泌升高，以响应t细胞有丝分裂刺激；ii)针对常见空气过敏原的过敏原特异性IgE水平降低，过敏原特异性IgG4水平升高；并且，iii)过敏性鼻炎和哮喘的风险持续降低。具体目标包括分析第一年室内宠物的数量，调整已建立的混杂因素和效果调节剂，对以下方面的持续影响：i) t细胞内细胞因子IL-4， ifn - γ和IL-10水平；ii)血清过敏原特异性IgE（猫、狗、尘螨、豚草、草和交替虫）和过敏原特异性IgG4（猫、狗、草和尘螨）水平；Iii)自我报告和医生诊断的过敏性鼻炎和哮喘的当前和终生病史。在上述分析中，我们还将iv)研究这些结果之间的关系，v)评估生物标志物的作用和每个亲本的特应性史。方法：对CAS队列进行问卷调查和家访，随访年龄为18岁。受激T细胞因子分析、总IgE、血清过敏原特异性IgE和IgG4水平将被确定，队列受试者和家长将回答一份关于受试者和父母的变应性鼻炎和哮喘的症状和诊断史以及早期宠物暴露的问卷。来自父母和受试者的血液标本、DNA和mRNA将被放置在生物储存库中，用于未来的分子流行病学研究。

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.