Dust Mite, Cockroach and Cat Allergens: Asthma

描述（由申请人提供）：本补助金的总体目标是 了解室内过敏原在哮喘中的作用。这项研究的重要性 来自疾病的异常流行，即8%的人 人口，以及需要治疗的大量患者， 急性哮喘，即每年超过100万例。这些研究的核心 认为易感儿童的免疫反应[包括 IgE抗体（ab）、IgG ab、IgG 4 ab和Th 2细胞]依赖于暴露。 拟议的研究涉及流行病学、测量接触的技术， 对免疫反应的详细评估和对急性发作的研究。 关于免疫反应的性质，有两种截然不同的观点， 非过敏个体：（1）他们是无应答者（免疫无知）; 或者（2）他们已经做出了另一种形式的免疫反应。期间 在过去的两年里，人们已经清楚地看到，在家里养猫是一件很重要的事情。 与哮喘风险降低有关， 过敏原可以诱导不同的免疫应答，包括IgG和IgG 4 抗体，但不是IgE抗体。这种修饰的Th 2应答提供了一种机会， 研究：过敏原暴露与 哮喘的风险;过敏性疾病中对过敏原的免疫反应的性质 和非过敏个体;以及免疫应答的方面， 造成哮喘的风险。这些结果表明， 猫过敏原暴露与致敏呈钟形关系 对尘螨过敏原呈线性。建议的实验将集中在：（一） 分析暴露、血清抗体反应与 室内过敏原和哮喘风险的前瞻性研究， 儿童队列;（二）详细调查循环的反应， 使用天然过敏原、重组蛋白质的T细胞对螨和猫过敏原 和跨越每个分子的重叠肽。这些研究将 评价T细胞表位识别、体外细胞因子应答的差异 和细胞表面表型， 不同的免疫反应。(III)关系的探讨 过敏反应和哮喘急性发作，使用三种方法： 前瞻性随访患者;过敏性鼻炎的实验性鼻病毒攻击 和非过敏性个体;以及调查表现为 哮喘到急诊室或医院。所提出的研究具有重要意义 使用过敏原避免治疗哮喘的意义，或新的 过敏原特异性免疫治疗的策略。

DESCRIPTION (provided by applicant): The overall objective of this grant is to understand the role of indoor allergens in asthma. The importance of this study comes from the extraordinary prevalence of the disease, i.e. -8 percent of the population, and the very large numbers of patients who require treatment for acute asthma, i.e. more than 1 million cases per year. Central to these studies is the view that the immune response in susceptible children [which includes IgE antibodies (ab), IgG ab, IgG4 ab and Th2 cells] is dependent on exposure. The proposed studies involve epidemiology, techniques for measuring exposure, detailed evaluation of the immune response, and studies of the acute episodes. There are two contrasting views about the nature of the immune response in non-allergic individuals: (1) that they are non-responders (immune ignorance); or (2) that they have made an alternative form of immune response. During the last two years it has become clear that the presence of a cat in the home is associated with a decreased risk of asthma and that high exposure to cat allergen can induce a different immune response that includes IgG and IgG4 antibodies, but not IgE ab. This modified Th2 response provides an opportunity to investigate: the dose response relationship between allergen exposure and the risk of asthma; the nature of the immune response to allergens in allergic and non-allergic individuals; and the aspects of the immune response that create the risk of asthma. These results suggest that the dose response relationship between exposure and sensitization is bell-shaped for cat allergen and linear for dust mite allergen. The experiments proposed will focus on: (I) the analysis of the relationship between exposure, serum antibody responses to indoor allergens, and the risk of asthma in prospective studies on three cohorts of children; (II) detailed investigation of the response of circulating T cells to mite and cat allergens using natural allergens, recombinant proteins and overlapping peptides spanning each of the molecules. These studies will evaluate differences in T cell epitope recognition, cytokine responses in vitro and cell surface phenotype of T cells from subjects with different exposure and different immune responses. (III) Investigation of the relationship between allergic responses and acute episodes of asthma using three approaches: following patients prospectively; experimental rhinovirus challenge of allergic and non-allergic individuals; as well as investigating patients presenting with asthma to the Emergency Room or hospital. The studies proposed have important implications for asthma treatment using allergen avoidance, or for novel strategies for allergen specific immunotherapy.