Immune Mechanisms, Genetic and Environmental Factors Influencing Outcomes

食物过敏的定义是由免疫机制引起的对食物蛋白质的不良反应。 据估计，目前已有超过1200万美国人受到影响。美国疾病控制与预防中心2008年的一份报告显示，儿童死亡率上升了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/幼儿是最常见的(约2.5%)，通常会消失，尽管最近的报告表明 年龄在5岁以上的耐力越来越强。花生过敏现在影响到大约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 与牛奶和鸡蛋过敏不同，它是致命的，只有20%的患者能缓解。只有一个有限的 了解食物过敏发展过程中涉及的机制。治疗花生过敏 特别是，目前还不知道为什么只有某些过敏症患者才会患上这种过敏症，或者机制是什么。 对它的永恒性负责。能有效预防或逆转食物过敏的进展，免疫 将需要进行干预。此外，成功的战略很可能需要指向 那些具有可识别风险的人(例如，具有与花生过敏发展相关的生物标记物的人)。 这项多中心的纵向观察性研究于2008年3月完成登记。这一群体包括 512名婴儿最初年龄为3-15个月，可能对鸡蛋/牛奶过敏或中重度特应性皮炎，并 对鸡蛋或牛奶的皮肤过敏试验呈阳性，但目前已知的花生过敏。这些标准是 用来建立花生过敏风险增加的队列。已经有了一个 正在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 作为对照组，从他们的250名兄弟姐妹中获得。需要继续进行这项研究才能确定 花生、鸡蛋和牛奶过敏的临床病程。这些最终的临床结果将被用于描绘， 花生生长发育相关生物标志物和免疫变化的比较研究 过敏和鸡蛋和牛奶过敏的丧失，同时解决遗传和环境问题 影响。该队列还将作为嗜酸性食管炎儿童和 对于那些正在接受花生免疫疗法的人，如本联盟的其他项目中所述。这个 观察性研究将解决与两个特定目标相关的假设：1)评估免疫(T细胞， 体液、先天免疫)和遗传参数(Toll样受体基因、微丝蛋白基因 突变等)与花生过敏的发生和牛奶/鸡蛋的临床结局相关 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/鸡蛋过敏的临床结局。

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.