Sublingual Immunotherapy for Peanut Allergy

描述（由申请人提供）：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发生这种过敏，不会长大，并且有严重和结束生命的过敏反应的风险。目前迫切需要一种积极主动的治疗花生过敏的方法，我们沿着其他人正在开发特定类型的免疫疗法，使这些患者不再对花生过敏。这一提议的意义在于 基于我们的具有里程碑意义的研究，这些研究已经检查了花生舌下免疫疗法（SLIT）的效果，显示花生过敏患者在治疗时可以摄入的花生量显著增加，并且在某些情况下，当治疗停止时导致长期临床耐受。SLIT涉及在舌下给予少量（微克至毫克）过敏原提取物。它提供了一种治疗食物过敏的新方法，并且似乎非常适合几个原因，包括这种方法的上级安全性。在这个建议中，我们将建立在我们以前的工作所产生的初步数据，表明SLIT是可行的，安全的，但在老年花生过敏的儿童是有效的。这项提案的长期目标是开发一种治疗花生过敏的方法，以减少患者对花生意外过敏反应的可能性。本项目旨在了解这种治疗的机制，并回答研究问题：在12至48个月的新诊断的花生过敏儿童中，与安慰剂相比，每天4毫克花生SLIT维持治疗36个月是否会诱导功能耐受？具体目标1：确定SLIT诱导花生SLIT过敏受试者嗜碱性粒细胞和肥大细胞（MC）低反应性的机制。具体目标二：确定花生过敏原特异性CD 4 + T细胞频率和表型，以及与花生临床耐受性发展相关的Treg细胞的抑制功能。具体目标3：确定SLIT中花生特异性粘膜和全身体液免疫应答对临床耐受性的影响。这些研究将有助于我们确定脱敏状态的机制和持久性，以及SLIT后对食物耐受性的后续发展。花生过敏的治疗是迫切需要的，这些研究的完成将为SLIT和其他类型的治疗的发展提供强有力的科学基础，希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. -