Etiology of Pediatric Atopy

小儿特应性的病因学

• 批准号: 6897306
• 负责人: EDWARD M ZORATTI
• 金额: $ 65.22万
• 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/6897306
• 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生活的猫和狗暴露于对T细胞细胞因子特征的潜在持续作用，特应性的生物标记和临床特应疗法的临床植物（n = 835），底特律地区儿童期研究（CAS）（CAS），以及年龄达到18岁。该队列中已经收集了广泛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在有丝分裂原刺激的T细胞中，以及过敏性鼻炎和哮喘的当前或历史。假设：与暴露水平较低的受试者相比，在生命的第一年中高水平暴露于狗和猫的受试者将表现出：i）17岁时的免疫反应持续改变，以低IL-4/IFN-gamma比率较低的IL-4/IFN-GAMMA比，并升高IL- 10对T-Cell有差异二裂的促二菌性刺激的分泌升高； ii）降低过敏原的IgE水平，并增加对普通气溶性的过敏原特异性IgG4； iii）持续降低了过敏性鼻炎和哮喘的风险。具体目的包括分析生命的第一年中室内宠物的数量，调整成熟的混杂因子和效应修饰符，以持续影响：i）IL-4，IFN-GAMMA，IFN-GAMMA和IL-10的T细胞内细胞因子水平； ii）过敏原特异性IgE（猫，狗，尘螨，肉饼，草和替代品）和过敏原特异性IgG4（猫，狗，狗，草和尘螨）的血清水平； iii）自我报告和医生诊断出过敏性鼻炎和哮喘的当前和终生历史。我们还将iv）研究这些结果与v）在上述分析中评估生物标志物和特应性史的作用。方法：CAS队列将通过问卷调查和18岁的家庭访问进行跟进。将确定刺激的T细胞因子分析，总IgE和血清过敏原特异性IgE和IgG4水平，并将队列受试者和父母回答有关症状的受试者和父母史以及过敏性鼻炎和诊断哮喘和哮喘和早期生命早期宠物后宠物暴露的问卷。来自父母和受试者的血液标本，DNA和mRNA将被放置在生物座位上，以进行未来的分子流行病学研究。