Redefining the major peanut allergens

描述(申请人提供)：对花生的过敏反应是因为易感人群对花生产生异常反应，产生一种血浆蛋白IgE，该蛋白与肥大细胞和嗜碱性粒细胞上的高亲和力IgE受体FceRI结合。这种IgE可以被称为过敏原的特定花生蛋白交联，导致严重的过敏反应。九种花生蛋白已被确定为过敏原，因为它们结合了过敏者的IgE。其中3个，Ara h 1，Ara h 2和Ara h 3被称为花生的主要过敏原，因为它们能与Western blotts上的IgE结合，在RAST抑制试验中与IgE相互作用，并且通过体外和/或体内功能测定具有可测量的活性。根据我们的工作和其他人的工作，我们现在知道arah2是这些过敏原中最有效的。我们支持在我们帮助开发的功能分析中基于效力(而不仅仅是活性)来定义主要花生过敏原的概念。我们的最新数据检测了花生提取物的过敏性，这些提取物特别是去除了arah2，有力地表明，对于大多数严重的花生过敏患者，arah2的活性并不是花生的大部分过敏活性的原因。使用常规层析和蛋白质组学相结合，我们已经产生了一个相对较短的潜在花生过敏原的新名单。我们建议通过结合我们的功能分析和蛋白质组学的力量来扩展我们的努力来定量地确定主要的花生过敏原。在此过程中，我们将详细定义花生过敏患者肥大细胞激活最主要的花生过敏原。我们将使用花生过敏的小鼠模型在体内测试我们的体外发现。这种方法，我们将确定花生中最有效的主要过敏原，有可能彻底改变我们的想法，即哪些花生过敏原对特定患者的过敏反应最重要。 公共卫生声明：花生过敏反应是一个主要的健康问题，目前的治疗方法不足以解决这个问题。我们对花生过敏的分子基础的了解是不完整的。该项目旨在使用功能分析和蛋白质组学来确定花生中最容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.