权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Mechanisms of Clinical Reactivity or Tolerance to Mouse Allergen

对小鼠过敏原的临床反应或耐受机制

基本信息

批准号：
8081806
负责人：
WAYNE G SHREFFLER
金额：
$ 77.62万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-06-11 至 2015-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8081806
关键词：
Address Allergens Allergic Allergic Disease Antibody Formation Antibody Repertoire Antigen-Presenting Cells B-Lymphocyte Epitopes Baltimore Basophils Blocking Antibodies Breathing Cell physiology Cells Cities Clinical Clinical Sensitivity Cohort Studies Communities Complex Data Development Disease Dose Effector Cell Enrollment Enzyme-Linked Immunosorbent Assay Epitopes Exhalation Exposure to Foundations Frequencies Helminths Human Hypersensitivity Hypersensitivity skin testing IgE IgG4 Immediate hypersensitivity Immune Immune Tolerance Immune response Immunoassay Immunoglobulin G Immunologics Immunotherapy In Vitro Individual Infection Interleukin-10 Investigation Knowledge Life Longitudinal Studies Maps Measures Mediating Modeling Modification Monitor Mus Natural History Nitric Oxide Occupational Outcome Participant Pathogenesis Peptides Phenotype Pneumonia Population Population Study Prevention Prevention strategy Preventive Preventive Intervention Primary Prevention Production Prospective Studies Recruitment Activity Regulatory T-Lymphocyte Relative (related person)Research Research Personnel Respiratory physiology Risk Risk Marker Role Sampling Secondary Prevention Serum Symptoms T-Lymphocyte Testing The Jackson Laboratory Therapeutic Therapeutic Intervention Time air sampling airborne allergen atopy clinical phenotype cohort community setting desensitization environmental allergen experience high risk in vivo inner city insight interest member novel prevent prospective protective effect public health relevance research study response role model translational study treatment strategy uptake

项目摘要

DESCRIPTION (provided by investigator): Although there has been a great deal of investigation into the pathogenesis of the allergic immune response, there is very little understanding of how natural allergen exposure influences the ensuing allergen-specific immune responses, and whether atopic disposition modifies allergen exposure-immune response relationships. In the proposed study, an occupational model of allergen exposure will be used to test the overarching hypothesis that the level of natural exposure to mouse allergen influences the subsequent immune responses to the major mouse allergen, Mus m 1, and ultimately, the clinical allergy phenotype. To test these hypotheses, we will continue to follow workers at The Jackson Laboratory (TJL) who are currently enrolled in a prospective cohort study, the JAXCohort Study, and recruit additional new workers into the cohort. The specific aims are as follows: (1) To continue to repeatedly assess mouse allergen exposure, mouse allergen-specific humoral responses, and clinical allergy phenotype in currently and newly enrolled participants; (2) To assess the diversity of IgG, IgG4, and IgE mouse allergen epitope repertoires among current and newly enrolled participants; (3) To assess mouse-specific Tr1 cell frequency in newly enrolled participants; and (4) To assess IgE-mediated function by assessing basophil phenotypes and Mus m 1 uptake by antigen presenting cells in newly IgE-sensitized cohort members. We will examine relationships between allergen exposure levels and these allergen-specific immune responses and clinical allergy phenotype. The proposed prospective cohort study, in a setting in which repeated assessments of personal allergen exposure are feasible, is arguably the best approach to understanding these complex, time- and exposure-dependent relationships. Findings from this study will result in a better understanding of the natural history of allergen exposure and immune responses that will provide a foundation for the development of immunomodulatory strategies aimed at prevention and treatment of allergic diseases. PUBLIC HEALTH RELEVANCE: A more detailed understanding of the relationship between allergen exposure and disease is needed to develop better preventive and treatment strategies. We will take advantage of the ability to study dose-response relationships more precisely in an occupational setting as a model to address this relationship. We will compare aspects of our findings in these workers to people with mouse allergy living with high levels of allergen in inner city Baltimore in the hope that the knowledge gained from this study will provide the foundation upon which to devise preventive and therapeutic interventions in occupational and community settings.

描述(由研究人员提供)：虽然对过敏免疫反应的发病机制进行了大量的调查，但对自然过敏原暴露如何影响随后的过敏原特异性免疫反应，以及特应性处置是否改变过敏原暴露-免疫反应关系的了解很少。在这项拟议的研究中，将使用过敏原暴露的职业模型来检验最重要的假设，即自然暴露于小鼠变应原的水平影响随后对主要小鼠变应原Mus m1的免疫反应，并最终影响临床变态反应表型。为了验证这些假设，我们将继续跟踪杰克逊实验室(TJL)目前正在进行的前瞻性队列研究--JAXCohort研究的工作人员，并招募更多的新工人加入队列。具体目标如下：(1)继续重复评估当前和新登记参与者中的小鼠过敏原暴露、小鼠过敏原特异性体液反应和临床过敏表型；(2)评估当前和新登记参与者中免疫球蛋白G、IgG4和IgE小鼠过敏原表位谱系的多样性；(3)评估新登记参与者中小鼠特异性TR1细胞频率；以及(4)通过评估新IgE致敏队列成员中嗜碱性粒细胞表型和抗原提呈细胞对Mus m1的摄取来评估IgE介导的功能。我们将研究过敏原暴露水平与这些过敏原特异性免疫反应和临床过敏表型之间的关系。在重复评估个人过敏原暴露是可行的情况下，拟议的前瞻性队列研究可以说是理解这些复杂的、依赖时间和暴露的关系的最佳方法。这项研究的结果将有助于更好地了解过敏原暴露和免疫反应的自然历史，这将为开发旨在预防和治疗过敏性疾病的免疫调节策略提供基础。公共卫生相关性：需要更详细地了解过敏原暴露与疾病之间的关系，以制定更好的预防和治疗策略。我们将利用在职业环境中更精确地研究剂量-反应关系的能力作为解决这种关系的模型。我们将在这些工作者身上与巴尔的摩市中心生活着高过敏原水平的老鼠过敏患者进行比较，希望从这项研究中获得的知识将为在职业和社区环境中制定预防和治疗干预措施提供基础。