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: 8302202
• 负责人: SCOTT H SICHERER
• 金额: $ 85.98万
• 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/8302202
• 关键词: 5 year old; Address; Adverse reactions; Affect; Age; Allergy to eggs; Allergy to peanuts; American; Atopic Dermatitis; Biological Markers; 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.

食物过敏被定义为由免疫机制引起的对食物蛋白质的不良反应， 目前估计影响超过 1200 万美国人。 2008 年 CDC 的一份报告显示，儿童时期的患病率增加了 18% 1997 年至 2007 年期间，估计有 3.9% 的儿童受到食物过敏的影响。牛奶或鸡蛋过敏 婴儿/幼儿最常见（约 2.5%），并且通常会得到解决，尽管最近的报告表明 5岁以上坚持不懈。花生过敏现在影响大约 1% 的幼儿， 这是十多年前报告的患病率的两倍。花生过敏通常很严重，有时 与牛奶和鸡蛋过敏相比，这种过敏是致命的，只有 20% 的患者能够得到缓解。只有有限的 了解食物过敏发展过程中涉及的机制。对于花生过敏 特别是，目前尚不清楚为什么只有某些特应性个体才会出现这种过敏，也不知道其机制是什么 对其永久性负责。为了有效预防或逆转食物过敏的进展，免疫 需要进行干预。此外，成功的战略可能需要针对 那些具有可识别风险的人（例如，具有与花生过敏相关的生物标志物的人）。 这项多中心、纵向观察性研究于 2008 年 3 月完成入组。该队列包括 512 名 3-15 个月大的婴儿可能患有鸡蛋/牛奶过敏或中度至重度特应性皮炎，并且患有 对鸡蛋或牛奶过敏点刺试验呈阳性，但目前没有已知的花生过敏。这些标准是 被用来建立一个患有或发展花生过敏风险增加的队列。已经有一个 持续进行的系列过敏评估的保留率为 98%。临床信息和 DNA 样本也被 从他们的 250 个兄弟姐妹中获得作为对照组。需要继续这项研究来确定 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， 比较和对比与花生发育相关的生物标志物和免疫变化 过敏和鸡蛋和牛奶过敏的损失，同时解决遗传和环境问题 影响。该队列还将作为嗜酸性粒细胞性食管炎儿童的比较组 对于那些接受花生免疫治疗的人，如本联盟其他项目中所述。这 观察性研究将提出与 2 个具体目标相关的假设：1）评估免疫（T 细胞、 体液免疫、先天免疫）和遗传参数（Toll 样受体多态性、聚丝蛋白基因 突变等）与花生过敏的发生和牛奶/鸡蛋的临床结果相关 过敏，以及 2) 评估环境（饮食、卫生相关）和临床（特应性皮炎）因素 可能会影响花生过敏的发生和牛奶/鸡蛋过敏的临床结果。