Establishing Precursors of Food Allergy in Newborns

描述（由申请人提供）：食物过敏（FA）是一种由免疫球蛋白（IG）E介导的食物超敏反应引起的疾病，在美国是一个日益严重的临床和公共卫生问题。大多数儿童FA发生在生命的最初几年，但缺乏专门设计用于识别美国大规模人群中FA产前前体的前瞻性出生队列研究。虽然阳性家族史是公认的过敏性疾病的预测因子，但可以调节个体对FA易感性的特定遗传标记仍在很大程度上未被探索。本申请的中心重点是利用波士顿出生队列的广泛资源，调查与FA发展相关的产前和遗传因素。该队列由约6，000名新生儿及其母亲组成，他们在波士顿医学中心登记或正在登记。最初招募时收集的信息包括产前流行病学和临床变量、出生结局以及母体和脐带血样本。该队列从出生起就接受了前瞻性随访，以识别FA和其他过敏性疾病的发生病例。在产后随访时收集的信息包括FA问卷;总的和食物和空气过敏原特异性IgE;医疗记录，包括医生诊断的ICD代码;和儿童的静脉血样本。为了最大限度地提高成本效益，将使用巢式病例对照设计，包括从波士顿出生队列中确定的总计400例FA事件病例和800例无症状和非致敏对照。本研究的主要目的是：（1）评估产前因素与头两年FA发生的相关性;（2）评估候选基因多态性与头两年FA发生的相关性。本研究将基于现有文献重点关注参与FA重要免疫途径的有希望但未经证实的候选基因，包括抗原呈递; IgE受体;先天免疫; TH 1偏斜; TH 2偏斜; TH 17偏斜; T调节;炎症;趋化因子;和其他。本研究具有以下优点：（1）通过使用大的现有出生队列和嵌套病例对照设计，具有很高的成本效益;（2）前瞻性数据收集，可以建立时间关系，并为因果关系提供强有力的证据;（3）检查全面的产前和遗传前体的能力;（4）大样本量，确保有足够的能力检测因果关系;（5）创新的基因-环境方法和利用最先进的高通量基因分型技术和统计方法;（6）一个高度互动和经验丰富的研究团队，在该出生队列和其他人群中进行分子和遗传研究方面有成功的记录，以及（7）FA未来研究的巨大潜力，因为我们有完善的基础设施和资源。这项研究将有助于开发一种新的和有前途的范例，以确定新生儿在儿童早期发展FA的高风险，这可能导致干预措施，防止或减轻FA以后的生活。食物过敏正在成为美国的一个主要临床和公共卫生问题;并且是因可能致命的过敏反应而急诊室就诊的最常见原因。大多数FA病例发生在生命的最初几年，但产前和遗传对FA发生的影响数据很少，这将是本研究的重点。

DESCRIPTION (provided by applicant): Food allergy (FA), a condition caused by an immunoglobulin (Ig) E-mediated hypersensitivity reaction to food, is a growing clinical and public health problem in the U.S. Most childhood FA develops in the first few years of life, but there is a lack of a prospective birth cohort study that is specifically designed to identify prenatal precursors of FA in a large U.S. population. While a positive family history is a well-recognized predictor of allergic diseases, specific genetic markers that can modulate individual susceptibility to FA remain largely unexplored. The central focus of this application is to investigate prenatal and genetic factors in relation to the development of FA, using the extensive resources of Boston Birth Cohort. This cohort consists of ~6,000 newborns and their mothers enrolled or being enrolled at the Boston Medical Center. The information collected at the initial recruitment included prenatal epidemiological and clinical variables, birth outcomes, and maternal and cord blood samples. This cohort has been prospectively followed from birth onward to identify incident cases of FA and other allergic diseases. The information collected at postnatal follow-ups includes FA questionnaires; total and food- and aero-allergen-specific IgE; medical records including ICD codes of physician diagnosis; and child's venous blood sample. To maximize cost-efficiency, a nested case-control design will be used, including a total of 400 FA incident cases and 800 non-symptomatic and non-sensitized controls identified from the Boston Birth Cohort. This study's primary aims are: (1) To assess the association of prenatal factors with development of FA in the first two years of life; and (2) To assess the association of candidate gene polymorphisms with development of FA in the first two years of life. This study will focus on promising yet unproven candidate genes involved in the important immune pathways of FA based on current literature, including Antigen presentation; IgE receptor; Innate immunity; TH1 skewing; TH2 skewing; TH17 skewing; T-Regulatory; Inflammatory; Chemokines; and Others. This study has following strengths:(1) highly cost-efficient by using a large, existing birth cohort and a nested case-control design; (2) a prospective data collection that can establish temporal relationships, and provide strong evidence for cause-and-effect; (3) a capability of examining a comprehensive array of prenatal and genetic precursors of FA; (4) a large sample size that assures adequate power to detect causal relations; (5) an innovative gene-environment approach and utilization of the state-of-the-art high-throughput genotyping technology and statistical methods; (6) a highly interactive and experienced research team with a successful track record in conducting molecular and genetic research in this birth cohort and in other populations, and (7) a tremendous potential for future studies of FA, given the well-established infrastructure and resources. This study will help develop a novel and promising paradigm to identify newborns at high risk of developing FA in early childhood, which may lead to interventions that prevent or mitigate FA later in life. Food allergy is emerging as a major clinical and public health problem in the US; and is the most common cause of emergency room visits for anaphylaxis which could be fatal. Most cases of FA developed in the first few years of life; but there is a sparse data on prenatal and genetic influence on the development of FA, which will be the focus of this study.