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）：我们的目标是研究生命早期猫和狗的暴露与对 T 细胞细胞因子谱、特应性生物标志物和特征明确的出生队列中的临床特应性的潜在持续影响之间的关系。 =835)，底特律地区儿童过敏研究 (CAS)，当他们年满 18 岁时。已经收集了该队列的大量早期环境暴露数据。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 和丝裂原刺激的 T 细胞中的干扰素 (IFN) γ，以及过敏性鼻炎和哮喘的当前或病史。假设：与低水平暴露的受试者相比，那些在出生后第一年高水平暴露于狗和猫的受试者将表现出： i) 17 岁时免疫反应持续改变，以低 IL-4/IFN 为代表[0100]-响应T细胞促有丝分裂刺激的γ比和IL-10分泌升高； ii) 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 水平增加； iii) 持续降低过敏性鼻炎和哮喘的风险。具体目标包括分析出生第一年的室内宠物数量，调整已确定的混杂因素和效应调节剂，以了解对以下方面的持续影响： i) T 细胞细胞内细胞因子 IL-4、IFN-γ 和 IL 水平-10； ii) 过敏原特异性 IgE（猫、狗、尘螨、豚草、草和链格孢）和过敏原特异性 IgG4（猫、狗、草和尘螨）的血清水平； iii) 自我报告和医生诊断的过敏性鼻炎和哮喘的当前和一生病史。我们还将 iv) 研究这些结果之间的关系，以及 v) 评估生物标志物的作用和上述分析中每位父母的特应性病史。方法：CAS 队列将在 18 岁时通过问卷调查和家访进行随访。将确定刺激 T 细胞细胞因子分析、总 IgE 以及血清过敏原特异性 IgE 和 IgG4 水平，队列受试者和家长将回答一份有关受试者和家长症状史、过敏性鼻炎和哮喘诊断以及早期宠物暴露后的调查问卷。来自父母和受试者的血液样本、DNA 和 mRNA 将被放置在生物样本库中，用于未来的分子流行病学研究。