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：
8308660
负责人：
WAYNE G SHREFFLER
金额：
$ 76.63万
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/8308660
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（由研究者提供）：尽管已经对过敏性免疫反应的发病机理进行了大量研究，但对天然过敏原暴露如何影响随之而来的过敏原特异性免疫反应以及特应性倾向是否改变过敏原暴露于免疫反应的关系，几乎没有了解。在拟议的研究中，将使用过敏原暴露的职业模型来检验总体假设，即自然暴露于小鼠过敏原会影响随后对主要小鼠过敏原的免疫反应，MUS M 1，最终是临床过敏表型。为了检验这些假设，我们将继续关注杰克逊实验室（TJL）的工人，他们目前正在参加一项前瞻性队列研究，JaxCohort研究，并招募更多新工人加入该队列。具体目的如下：（1）继续反复评估小鼠过敏原暴露，小鼠过敏原特异性体液反应以及当前和新招募的参与者的临床过敏表型；（2）评估当前和新招收的参与者中IgG，IgG4和IgE小鼠表位曲目的多样性；（3）评估新招募的参与者中小鼠特异性的TR1细胞频率；（4）通过评估新近含IgE敏感的队列成员中抗原呈现细胞的base粒表型和MUS M 1摄取来评估IgE介导的功能。我们将检查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。拟议的前瞻性队列研究是在对个人过敏原暴露的重复评估的环境中，可以说是理解这些复杂，时间和暴露依赖性关系的最佳方法。这项研究的结果将使人们更好地了解过敏原暴露和免疫反应的自然史，这将为发展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：需要对过敏原暴露与疾病之间的关系有更详细的了解，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，以此作为解决这种关系的模型。我们将将这些工人的发现的各个方面与在巴尔的摩内城过敏原的老鼠过敏的人的各个方面，希望从这项研究中获得的知识为在职业和社区环境中设计预防和治疗性干预措施的基础。