Redefining the major peanut allergens

描述（由申请方提供）：对花生过敏反应的发生是因为易感个体通过产生血浆蛋白IgE对花生产生异常反应，IgE与肥大细胞和嗜碱性粒细胞上的IgE高亲和力受体FceRI结合。这种IgE可以被称为过敏原的特定花生蛋白质交联，导致严重的过敏反应。九种花生蛋白质已被确定为过敏原，因为它们结合过敏个体的IgE。其中三种，Ara h 1，Ara h 2和Ara h 3被称为主要的花生过敏原，这是基于它们在Western印迹上结合IgE，在RAST抑制测定中与IgE相互作用，以及通过体外和/或体内功能测定评估具有可测量的活性的能力。根据我们的工作和其他人的工作，我们现在知道Ara h 2是这些过敏原中最有效的。在我们帮助开发的功能性检测中，我们支持根据效力（而不仅仅是活性）定义主要花生过敏原的概念。我们对专门去除Ara h 2的花生提取物的过敏性进行检查的最新数据强烈表明，对于大多数严重花生过敏的患者来说，Ara h 2的活性并不能解释花生的大部分过敏活性。使用传统的色谱结合蛋白质组学，我们已经产生了一个相对较短的名单，新的潜在的花生过敏原。我们建议扩大我们的努力，定量定义的主要花生过敏原，结合我们的功能检测与蛋白质组学的力量。在此过程中，我们将从分子上详细定义对花生过敏患者肥大细胞活化最负责任的花生过敏原。我们将使用花生过敏的小鼠模型在体内测试我们的体外研究结果。这种方法，我们将明确确定花生中最有效的主要过敏原，有可能完全改变我们的想法，即花生过敏原对特定患者的过敏反应最重要。 公共卫生声明：对花生的过敏反应是一个主要的健康问题，目前的治疗方法是不够的。我们对花生过敏的分子基础的知识是不完整的。该项目旨在使用功能测定和蛋白质组学来鉴定花生中最易引起易感人群过敏反应的分子。

DESCRIPTION (provided by applicant): Allergic reactions to peanuts occur because susceptible individuals have an aberrant response to peanuts by producing a plasma protein, IgE, that binds to the high affinity receptor for IgE, FceRI, on mast cells and basophils. This IgE can be cross-linked by specific peanut proteins, called allergens, leading to a severe allergic reaction. Nine peanut proteins have been identified as allergens because they bind IgE from allergic individuals. Three of these, Ara h 1, Ara h 2, and Ara h 3 are called the major peanut allergens based on their ability to bind IgE on Western blots, to interact with IgE in RAST-inhibition assays, and to have measurable activity as assessed by in vitro and/or in vivo functional assays. Based on our work and the work of others, we now know that Ara h 2 is the most potent of these allergens. We have championed the concept of defining the major peanut allergens based on potency (not just activity) in functional assays that we have helped to develop. Our newest data examining the allergenicity of peanut extracts that have been specifically depleted of Ara h 2 demonstrate strongly that, for most severely peanut allergic patients, the activity of Ara h 2 does not account for the majority of the allergenic activity of peanuts. Using conventional chromatography combined with proteomics we have generated a relatively short list of new potential peanut allergens. We propose to extend our efforts to define quantitatively the major peanut allergens by combining our functional assays with the power of proteomics. In doing this we will define in molecular detail the peanut allergens most greatly responsible for mast cell activation in peanut allergic patients. We will test our in vitro findings in vivo using a mouse model of peanut allergy. This approach, in which we will definitively identify the most potent major allergens in peanuts has the potential to completely change our thinking as to which peanut allergens are the most important for allergic reactions in specific patients. Public Health Statement: Allergic reactions to peanuts are a major health problem for which current treatments are inadequate. Our knowledge of the molecular basis of peanut allergy is incomplete. This project is designed to use functional assays and proteomics to identify the molecules in peanuts that are most responsible for allergic reactions in susceptible persons.