Etiology of Pediatric Atopy

小儿特应性的病因学

• 批准号: 6823518
• 负责人: EDWARD M ZORATTI
• 金额: $ 67.85万
• 依托单位: HENRY FORD HEALTH SYSTEM
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6823518
• 关键词: adolescence (12-20); allergens; asthma; biomarker; clinical research; disease /disorder etiology; domestic animals; early experience; environmental exposure; family genetics; gene environment interaction; genetic registry /resource /referral center; helper T lymphocyte; human subject; immune response; immunoglobulin E; immunoglobulin G; interferon gamma; interleukin 10; interleukin 4; leukocyte activation /transformation; questionnaires; respiratory disorder epidemiology; rhinitis; tissue resource /registry

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.

描述(由申请人提供)：我们的目标是研究早期猫和狗暴露在潜在的持续影响T细胞细胞因子谱，特应性生物标记物和临床特应性之间的关系，在一个具有良好特征的出生队列(n=835)，底特律地区儿童过敏研究(CAS)，当他们达到18岁。关于这个队列，已经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(干扰素)伽马，以及过敏性鼻炎和哮喘的当前或历史。假设：与低水平暴露的受试者相比，那些在出生第一年高水平暴露于猫狗的受试者将表现出：i)17岁时持续改变的免疫反应，表现为低IL-4/干扰素-γ比率和对T细胞有丝分裂刺激的IL-10分泌增加；ii)过敏原特异性IgE水平降低，常见空气过敏原特异性IgG4增加；以及iii)过敏性鼻炎和哮喘的风险持续降低。具体目标包括分析出生第一年的室内宠物的数量，调整公认的混杂因素和效果修饰物，以确定对以下方面的持续影响：i)T细胞细胞内细胞因子IL-4、干扰素-γ和IL-10的水平；ii)血清过敏原特异性IgE(猫、狗、尘螨、豚草和交链孢霉)和过敏原特异性IgG4(猫、狗、草和尘螨)的水平；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。我们还将研究这些结果之间的关系，以及v)在上述分析中评估生物标记物和特应性病史在每个父母中的作用。方法：在18岁时对CAS队列进行问卷调查和家访。刺激T细胞细胞因子分析、总IgE和血清过敏原特异性IgE和IgG4水平将被测定，队列受试者和父母将回答一份关于受试者和父母症状和过敏性鼻炎和哮喘的诊断以及早期接触宠物的问卷。来自父母和受试者的血液样本、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。