Clinical Research Unit: Johns Hopkins University

摘要/摘要 花生过敏很常见，影响到1%-2%的儿童，与大多数其他儿童食物过敏相反， 通常会持续终生。更令人担忧的是，花生流行的原因尚不清楚 过敏症在过去的20年里增加了2-3倍。虽然Leap的研究令人信服地证明了花生 大约80%的高危婴儿可以通过早期引入花生来预防过敏，重要的是要 认识到早期引进花生在预防花生过敏方面并不是普遍成功的。为 例如，2%的登记婴儿已经过敏，定义为在研究中口服花生挑战失败 另有11%的人根据大花生皮试被认为是过敏的，因此 被排除在基线挑战之外。早发性花生过敏症婴儿的这种表型 不仅从临床角度来看，这是一种未得到满足的需求，因为大多数人会终身对花生过敏， 它们也为研究食物过敏发展的潜在机制提供了一个独特的机会。 在这个项目中，我们将有机会从临床和机械两方面描述这些婴儿的特征。 立场，将他们与没有花生过敏或没有花生过敏的同龄人进行比较 过敏。然后，作为我们的主要目标，我们将研究花生口服免疫疗法的安全性和有效性。 队列，据我们所知，这将是最早开始任何形式的特异性免疫疗法 食物过敏的治疗。我们将通过以下具体目标来实现这一目标：1)开展双 4-11个月大花生过敏婴儿花生油的盲法、安慰剂对照(DBPC)研究。我们 假设在这么小的年龄进行治疗将是安全有效的，不仅会导致高发病率 脱敏也是持续性无反应(SU)，远远高于老年人的表现 儿童和青少年。2)描述早发性花生过敏婴儿的特征，或被认为 花生过敏的高危人群，在这项研究中，他们将分为三个不同的类别 亚组：不对花生过敏或对花生过敏的人，对花生过敏但不过敏的人，以及 在招募时已经出现临床花生过敏症的患者。3)与 生物标记基金和机会基金的调查人员将仔细挑选样本以获得更详细的信息 机制研究，可能包括新陈代谢组学、微生物组学、表观基因组学和细胞飞行时间 在AIM 1的免疫学分析中使用的常见生物标志物。我们相信OIT试验将有一个 对未来花生和其他食物过敏的治疗产生了深远的影响，这项研究将高度重视 在确定花生发育中最重要的临床和免疫学因素方面提供信息 过敏。

Abstract / Summary Peanut allergy is common, affecting 1-2% of children, and as opposed to most other childhood food allergies, usually persists lifelong. Even more concerning, for reasons that are not yet clear the prevalence of peanut allergy has increased 2-3 fold in the last 20 years. While the LEAP study convincingly demonstrated that peanut allergy could be prevented in about 80% of high risk infants by early peanut introduction, it is important to recognize that early peanut introduction is not universally successful in the prevention of peanut allergy. For example, 2% of the enrolled babies were already allergic, defined by a failed oral peanut challenge at study entry, and an additional 11% were assumed to be allergic based on a large peanut prick skin test and therefore excluded from the baseline challenge. This phenotype of babies with exceptionally early onset peanut allergy not only presents an unmet need from a clinical standpoint, since most will go on to have lifelong peanut allergy, they also provide a unique opportunity to study the underlying mechanisms for the development of food allergy. In this project, we will have the opportunity to characterize these infants from both a clinical and mechanistic standpoint, comparing them to their peers who have either no peanut sensitization or sensitization without allergy. Then, as our primary aim, we will study the safety and efficacy of peanut oral immunotherapy in this cohort, which to our knowledge will be the earliest initiation of any form of specific immunotherapy for the treatment of food allergy. We will accomplish this through the following specific aims: 1) To conduct a double- blind, placebo-controlled (DBPC) study of peanut OIT in 4 to 11 month old infants with peanut allergy. We hypothesize that treatment at this early age will be safe and effective, inducing not just a high rate of desensitization but also of sustained unresponsiveness (SU), far higher than has been demonstrated in older children and adolescents. 2) To characterize a cohort of infants with early onset peanut allergy, or deemed to be at high risk for the development of peanut allergy, who will be categorized for this study into three distinct subsets: those who are not peanut sensitized or allergic, those who are sensitized but not allergic, and those who have already developed clinical peanut allergy at the time of recruitment. 3) To collaborate with the investigators of the Biomarker Facility and Opportunity Fund to carefully select samples for more detailed mechanistic studies, potentially including metabolomics, microbiomics, epigenomics, and CyTOF, in addition to the usual biomarkers to be used in the immunologic profiling in Aim 1. We believe that the OIT trial will have a profound impact on the future treatment of peanut and other food allergies, and that this study will be highly informative in defining the clinical and immunologic factors that are most important in the development of peanut allergy.