Immune Mechanisms, Genetic and Environmental Factors Influencing Outcomes

影响结果的免疫机制、遗传和环境因素

• 批准号: 8505358
• 负责人: SCOTT H SICHERER
• 金额: $ 80.74万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8505358
• 关键词: 5 year old; Address; Adverse reactions; Affect; Age; Allergy to eggs; Allergy to peanuts; American; Atopic Dermatitis; Biological Markers; Centers for Disease Control and Prevention (U.S.); Child; Childhood; Clinical; Control Groups; DNA; Development; Diet; Enrollment; Environmental Risk Factor; Eosinophilic Esophagitis; Food; Food Hypersensitivity; Gene Mutation; Genetic; Genetic Polymorphism; Hygiene; Hypersensitivity; Immune; Immunobiology; Immunologics; Immunotherapy; Individual; Infant; Intervention; Milk; Milk Hypersensitivity; Natural Immunity; Observational Study; Outcome; Patients; Peanuts - dietary; Persons; Prevalence; Proteins; Reporting; Risk; Sampling; Siblings; T-Lymphocyte; Toll-like receptors; cohort; egg; filaggrin; prevent; skin prick test

Food allergy is defined as an adverse reaction to food proteins caused by immunologic mechanisms and is now estimated to affect over 12 million Americans. A 2008 CDC report indicated an 18% rise in childhood food allergy from 1997-2007 with an estimated 3.9% of children currently affected. Milk or egg allergies in infants/young children are most common (~2.5%), and typically resolve, although recent reports indicate increasing persistence beyond age 5 years. Peanut allergy now affects approximately 1% of young children, which is double the prevalence reported just over a decade ago. Peanut allergy is often severe, sometimes fatal and, in contrast to milk and egg allergy, resolves in only 20% of patients. There is only a limited understanding of the mechanisms involved in the developmental course of food allergies. For peanut allergy in particular, it is not known why only certain atopic individuals acquire this allergy, or what mechanisms are responsible for its permanence. To effectively prevent or reverse the progression of food allergy, immune interventions will be needed. Furthermore, it is likely that successful strategies will need to be directed to those persons at identifiable risk (e.g., who have biomarkers associated with development of peanut allergy). This multi-center, longitudinal observational study completed enrollment in March 2008. The cohort includes 512 infants initially age 3-15 months with likely egg/milk allergy or moderate-severe atopic dermatitis and a positive allergy prick skin test to egg or milk, but without current known peanut allergy. These criteria were employed to establish a cohort with an increased risk to have or develop peanut allergy. There has been a 98% retention rate for ongoing serial allergy assessments. Clinical information and DNA samples were also obtained from 250 of their siblings as a control group. Continuation of this study is required to determine the clinical course of peanut, egg and milk allergies. These final clinical outcomes will be used to delineate, compare and contrast biologic markers and immunologic changes associated with development of peanut allergy and loss of egg and milk allergy, while simultaneously addressing genetic and environmental influences. This cohort will also serve as a comparator group for children with eosinophilic esophagitis and for those undergoing immunotherapies to peanut as described in additional projects in this Consortium. The observational study will address hypotheses associated with 2 specific aims: 1) To evaluate immune (T cell, humoral, innate immunity) and genetic parameters (Toll-like receptor polymorphisms, filaggrin gene mutations, and others) associated with the occurrence of peanut allergy and clinical outcomes for milk/egg allergy, and 2) To evaluate environmental (diet, hygiene-related) and clinical (atopic dermatitis) factors that may influence occurrence of peanut allergy and clinical outcomes for milk/egg allergy.

食物过敏被定义为对由免疫机制引起的食物蛋白的不利反应，IS 现在估计会影响超过1200万美国人。 2008年CDC报告表明童年增长了18％ 1997 - 2007年的食物过敏，目前估计有3.9％的儿童受到影响。牛奶或鸡蛋过敏 婴儿/幼儿最常见（约2.5％），通常是解决的，尽管最近的报告表明 超过5岁以上的持久性。花生过敏现在影响大约1％的幼儿， 这是十多年前报道的流行率的两倍。花生过敏通常很严重，有时 与牛奶和鸡蛋过敏相反，只有20％的患者可以解决。只有有限 了解食物过敏的发育过程中涉及的机制。用于花生过敏 特别是，尚不知道为什么只有某些特定的人会获得这种过敏，或者是什么机制 负责其永久性。有效防止或扭转食物过敏的进展，免疫 需要干预。此外，可能需要将成功的策略指向 那些处于可识别风险的人（例如，具有与花生过敏发展相关的生物标志物）。 这项多中心的纵向观察研究于2008年3月完成了入学率。该队列包括 512名婴儿最初可能3-15个月，可能卵/牛奶过敏或中度重度性皮炎和A 阳性过敏的皮肤测试对鸡蛋或牛奶，但没有当前已知的花生过敏。这些标准是 被用来建立具有增加或发展花生过敏风险的队列。有一个 持续的串行过敏评估的保留率为98％。临床信息和DNA样品也是 从250个兄弟姐妹作为对照组获得。需要这项研究的继续来确定 花生，鸡蛋和牛奶过敏的临床过程。这些最终的临床结果将用于描述， 比较和对比生物学标记和与花生发展相关的免疫学变化 鸡蛋和牛奶过敏的过敏和丧失，同时解决遗传和环境 影响。该队列还将作为嗜酸性食管炎儿童和 对于那些接受该财团的其他项目中所述的对花生进行免疫疗法的人。这 观察性研究将解决与2个特定目的相关的假设：1）评估免疫（T细胞， 体液，先天免疫）和遗传参数（Toll样受体多态性，Filaggrin基因 突变以及其他）与牛奶/鸡蛋的花生过敏和临床结果有关 过敏和2）评估环境（饮食，卫生相关）和临床（特应性皮炎）因素 可能影响牛奶/鸡蛋过敏的花生过敏和临床结果的发生。