Sublingual Immunotherapy for Peanut Allergy

描述(申请人提供)：花生过敏是最常见的食物过敏之一；大多数儿童在生命早期就会患上这种过敏，不会痊愈，并面临严重和致命的过敏反应的风险。迫切需要对花生过敏进行积极的治疗，我们正在与其他人一起开发特定类型的免疫疗法，使这些患者不再对花生过敏。这项提议的意义在于 基于我们对花生舌下免疫疗法(SIT)效果进行的里程碑式的研究，这些研究表明花生过敏患者在治疗期间可以摄入的花生数量大幅增加，在某些情况下，当停止治疗时会导致长期的临床耐受。SIIT涉及在舌头下给药少量(微克到毫克)的过敏原提取物。它提供了一种治疗食物过敏的新方法，似乎非常适合于几个原因，包括这种方法的卓越安全性。在这项提案中，我们将建立在我们之前的工作产生的初步数据的基础上，这些数据表明，SILT对年龄较大的花生过敏儿童是可行和安全的，但效果各不相同。这项建议的长期目标是开发一种治疗花生过敏的方法，以降低患者意外对花生过敏反应的可能性。为了了解这种治疗的机制，该项目将回答以下研究问题：在新诊断的12至48个月大的花生过敏儿童中，与安慰剂相比，36个月的维持治疗与每天4毫克的花生狭缝是否会诱导功能耐受？具体目标1：确定Sit引起花生过敏性受试者嗜碱性粒细胞和肥大细胞(MC)低反应性的机制。具体目标2：确定花生过敏原特异性的CD4+T细胞的频率和表型，以及Treg细胞的抑制功能，这与临床对花生的耐受性有关。具体目标3：确定花生特异性黏膜和系统体液免疫反应对临床耐受性的影响。这些研究将帮助我们确定脱敏状态的机制和持久性，以及随后对食物裂开后的耐受性的发展。花生过敏的治疗是迫切需要的，这些研究的完成将为Sit和其他类型的治疗方法的开发提供强有力的科学基础，这些疗法有望产生对花生和其他食物的长期临床耐受性。 -

DESCRIPTION (provided by applicant): Peanut allergy is one of the most common food allergies; most children develop this allergy early in life, do not outgrow it and are at risk for severe and life-ending anaphylactic reactions. There is a critical need for a proactive treatment for peanut allergy and we along with others are developing specific types of immunotherapy that will cause these patients to be no longer allergic to peanuts. The significance of this proposal is based on our landmark studies that have examined the effects of peanut sublingual immunotherapy (SLIT) showing a substantial increase in the amount of peanut that a peanut allergic patient can ingest while on therapy and in some cases causing long-term clinical tolerance when the therapy is discontinued. SLIT involves the administration of small amounts (micrograms to milligrams) of allergen extract under the tongue. It offers a novel means of treatment for food allergy and seems well suited for several reasons, including the superior safety of this approach. In this proposal, we will build on the preliminary data generated by our previous work showing that SLIT is feasible and safe but variably efficacious in older peanut-allergic children. The long-term goal of this proposal is the development of a treatment for peanut allergy that will lessen the likelihood of an accidental allergic reaction to peanuts in thee patients. With the following Aims designed to understand the mechanism of this treatment, this project will answer the research question: In newly diagnosed peanut-allergic children between the ages of 12 and 48 months, does 36 months of maintenance treatment with 4 milligrams per day of peanut SLIT induce functional tolerance, when compared to placebo? Specific Aim 1: Determine the mechanisms by which SLIT induces hyporesponsiveness in basophils and mast cells (MCs) in peanut allergic subjects on peanut SLIT. Specific Aim 2: Determine the peanut allergen-specific CD4+ T cell frequencies and phenotypes, as well as the suppressive function of Treg cells that are associated with the development of clinical tolerance to peanuts. Specific Aim 3: Determine the effect of peanut-specific mucosal and systemic humoral immune responses in SLIT on clinical tolerance. These studies will help us identify the mechanism and durability of the desensitized state and then the subsequent development of tolerance to foods after SLIT. A treatment for peanut allergy is critically needed the completion of these studies wil provide a strong scientific basis for the development of SLIT and other types of therapy that hope to produce long-term clinical tolerance to peanuts and other foods. -