Dust Mite, Cockroach and Cat Allergens in Asthma

描述（由申请人提供）：该基金的长期目标是了解室内环境在哮喘中的作用。这些研究的重要性来自于这种疾病的流行率（近6%的人口正在接受治疗）以及大量儿童和成人需要在急诊室或医院接受治疗的事实。这些研究将增加我们对过敏原蛋白质和其他空气传播颗粒成分与哮喘相关性的理解。一个主要问题已经提出了证据，定量高家庭暴露，从猫或狗的蛋白质与IgE抗体（ab）的患病率或滴度增加无关。相比之下，接触尘螨、蟑螂或花粉过敏原可诱导足够的IgE抗体，从而对血清总IgE做出重要贡献。这表明特定的过敏原可以对过敏性疾病的发展产生不同的影响。猫接触诱导的新型免疫反应的特征是高滴度IgG和IgG 4 ab，而没有IgE ab反应。这被描述为修饰的Th 2应答。有趣的是，可以诱导这种或其他形式耐受性的过敏原（即猫、狗、小鼠和大鼠）似乎都起源于哺乳动物。拟进行的实验将侧重于：1）在生活在不同环境中的儿童和成人队列中测定IgG和IgG 4抗体以及血清总IgE和IgE抗体。这些研究将研究对螨和猫的反应是否应被视为两类过敏原的代表;非哺乳动物（I类）和哺乳动物（II类）; 2）比较对蛋白质过敏原的IgE反应与新鉴定的对哺乳动物蛋白质上与过敏反应相关但与哮喘无关的碳水化合物表位的反应。3)对空气中携带过敏原的颗粒成分进行详细研究，包括过敏原含量分析，以及来自过敏原或细菌来源的内毒素和DNA定量。这些研究将与蛋白质和非蛋白质影响的研究相结合树突细胞和T细胞上的内毒素（即DNA或内毒素）成分; 4）调查与猫一起生活而没有症状的受试者，以了解a）在有或没有IgE ab的儿童中对高暴露的炎症和细胞因子反应，B）长期减少猫过敏原暴露对抗体和T细胞反应的影响;旨在了解耐受性反应是否依赖于持续高暴露的研究。总的来说，这些研究旨在回答室内环境的差异如何导致致敏、血清总IgE、哮喘的患病率和这种疾病的严重程度。先前和拟议中的研究与该补助金有关，旨在了解室内环境在哮喘中的作用。这包括详细研究为什么高暴露于某些过敏原（如猫和狗）的影响小于高暴露于非哺乳动物过敏原（如尘螨、蟑螂或花粉）的蛋白质和颗粒的影响。这些研究有助于理解这种疾病如此常见的原因，并有助于开发新的治疗方法。

DESCRIPTION (provided by applicant): The long term objective of this grant is to understand the role of the indoor environment in asthma. The importance of these studies comes from the prevalence of the disease, (almost 6% of the population are on treatment) and the fact that very large numbers of children and adults require treatment in emergency rooms or hospitals. The studies proposed will increase our understanding of the relevance to asthma of allergen proteins and of other constituents of the particles that become airborne. A major question has been raised by evidence that quantitatively high domestic exposures, to proteins derived from cat or dog are not associated with increased prevalence or titer of IgE antibodies (ab). By contrast, exposure to dust mite, cockroach or pollen allergens can induce sufficient IgE ab to make an important contribution to total serum IgE. This suggests that specific allergens can exert a different effect on the development of allergic disease. The novel immune response induced by cat exposure is characterized by high titer IgG and IgG4 ab without an IgE ab response. This has been described as a modified Th2 response. Interestingly it appears that the allergens that can induce this or other forms of tolerance i.e. cat, dog, mouse and rat, are all mammalian in origin. The experiments proposed will focus on: 1) Measurements of IgG and IgG4 ab, as well as total serum IgE and IgE ab to allergens in cohorts of children and adults living in different environments. These studies will investigate whether the response to mite and cat should be seen as representative of two classes of allergens; non-mammalian (Class I) and mammalian (Class II); 2) Comparison of IgE responses to protein allergens with the newly identified responses to a carbohydrate epitope on mammalian proteins that is associated with anaphylaxis but not with asthma. 3) Detailed studies on the constituents of the allergen-bearing particles that become airborne, including analysis of allergen content, as well as quantification of endotoxin and DNA derived either from the source of the allergen or from bacteria. These studies will be combined with studies on the effects of protein and non-protein (i.e. DNA or endotoxin) constituents on dendritic cells and T cells; 4) Investigation of subjects who have lived in a house with a cat without symptoms to understand a) the inflammatory and cytokine response to high exposure in children with or without IgE ab, b) the effects of a prolonged decrease of exposure to cat allergens on antibodies and T cells responses; studies that are designed to understand whether tolerant responses are dependent on continued high exposure. Overall the studies are designed to answer how differences in the indoor environment can contribute to sensitization, total serum IgE, the prevalence of asthma and the severity of this disease. The previous and proposed studies related to this grant are designed to understand the role of the indoor environment in asthma. This includes detailed investigation of the reasons why high exposure to some allergens e.g. cat and dog have less effect than high exposure to proteins and particles derived from non- mammalian allergens such as dust mites, cockroaches, or pollens. These studies are relevant to understanding the reasons why the disease is so common and to developing new approaches to treatment.