Immune Mechanisms, Genetic and Environmental Factors Influencing Outcomes

食物过敏是由免疫机制引起的对食物蛋白质的不良反应， 现在估计影响了超过1200万美国人2008年疾病控制和预防中心的一份报告显示， 1997年至2007年，食物过敏的儿童中估计有3.9%目前受到影响。牛奶或鸡蛋过敏 婴儿/幼儿最常见（约2.5%），通常会消退，尽管最近的报告表明 5岁以上的持续性增加。花生过敏现在影响大约1%的幼儿， 是十多年前报告的两倍。花生过敏往往是严重的，有时 与牛奶和鸡蛋过敏相反，这种过敏是致命的，只有20%的患者能痊愈。是有限 了解食物过敏发展过程中的机制。花生过敏 特别是，不知道为什么只有某些特应性个体获得这种变态反应，或者什么机制 对它的持久性负责。为了有效预防或逆转食物过敏的进展，免疫 将需要干预。此外，成功的战略可能需要针对 处于可识别风险的人员（例如，具有与花生过敏的发展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名最初年龄为3-15个月的婴儿，可能患有鸡蛋/牛奶过敏或中重度特应性皮炎， 对鸡蛋或牛奶过敏的皮肤点刺试验呈阳性，但目前没有已知的花生过敏。这些标准 用于建立具有增加的患有或发展花生过敏的风险的队列。出现了 正在进行的系列过敏评估的留存率为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。需要继续本研究以确定 花生鸡蛋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 影响。该队列还将作为嗜酸性食管炎儿童的对照组， 对于那些正在接受花生免疫治疗的人，如本联盟其他项目所述。的 观察性研究将解决与2个特定目的相关的假设：1）评价免疫（T细胞， 体液、先天免疫）和遗传参数（Toll样受体多态性、聚丝蛋白基因 突变和其他）与花生过敏的发生和牛奶/鸡蛋的临床结果相关 过敏，和2）评价环境（饮食，对甲苯相关）和临床（特应性皮炎）因素， 可能影响花生过敏的发生和牛奶/鸡蛋过敏的临床结果。

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.