Primary Immuno-Deficiencies Affecting Specific Stages of the Immune Response

影响免疫反应特定阶段的原发性免疫缺陷

• 批准号: 8296689
• 负责人: CORNELIS P TERHORST
• 金额: $ 180.82万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-05 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8296689
• 关键词: Primary; Immuno; Deficiencies; Affecting; Specific

This revised application for our new Program Project Grant brings together a group of investigators who are experts in the areas of molecular and cellular immunology and human and mouse genetics. We propose to study the role of single genes in the pathogenesis of X-linked Lymphoproliferative syndrome (XLP), Common variable immunodeficiency (CVID), Omenn syndrome and Severe Combined Immunodeficiencies (SCID) in an application, entitled: "Primary Immunodeficiencies Affecting Specific Stages of the Adaptive Immune Rresponse" Because of successful preliminary analyses of patient materials, exciting findings in genetically altered mice, this application seeks to define how mutations in the SH2D1A, SH2D1B/C, TACI, RAG-1/2, DNA Ligase IV or Cernunnos genes affect T and B cell development and T cell dependent and/or T cell-independent immunoglobulin responses. We will use our recently acquired insights into the causes of these diseases in the following four interlinked projects and an Administrative Core: Project #1 Role of the SAP (SH2D1A) gene in T cell-dependent antibody responses. Cox Terhorst, Beth Israel Deaconess Medical Center. Project #2 Role of in TACI mutations in Common Variable Immunodeficiency Raif Geha, Children's Hospital of Boston. Project #3 Gene knock-in models for Omenn syndrome and leaky SCID. Luigi Notarangelo, Children's Hospital of Boston. Project #4 Mouse Models of Severe Combined Immunodeficiencies. Fred Alt, Children's Hospital of Boston. Core A Administrative Core Cox Terhorst, Beth Israel Deaconess Medical Center. The outcomes of proposed studies should lead to better understanding of the complex and often alternate disease manifestations that are caused by mutations in a single gene. The results of these studies should suggest therapeutic strategies that can be applied to these PID patients and may unravel molecular and cellular mechanisms that are generally involved in immune dysregulation, autoimmunity and cancer.

我们对新计划项目的修订申请赠款汇集了一群调查人员 分子和细胞免疫学以及人类和小鼠遗传学领域的专家。我们建议 研究单基因在X连锁淋巴增生综合征（XLP）的发病机理中的作用，常见 可变免疫缺陷（CVID），Omenn综合征和严重的联合免疫缺陷（SCID）（SCID） 申请，标题为： “影响适应性免疫反应的特定阶段的原发性免疫缺陷” 由于对患者材料进行了成功的初步分析，因此在遗传改变的小鼠中的令人兴奋的发现， 该应用程序旨在定义SH2D1A，SH2D1B/C，TACI，RAG-1/2，DNA连接酶IV中的突变如何 或Cernunnos基因影响T和B细胞的发育以及T细胞依赖性和/或T细胞独立的 免疫球蛋白反应。我们将使用最近获得的见解来对这些疾病的原因 以下四个相互联系的项目和一个行政核心： SAP（SH2D1A）基因在T细胞依赖性抗体反应中的项目＃1的作用。 考克斯·特霍斯特（Cox Terhorst），贝丝以色列执事医疗中心。 项目＃2在TACI突变中的作用在常见可变免疫缺陷中 莱夫·盖哈（Raif Geha），波士顿儿童医院。 Omenn综合征和SCID泄漏的项目＃3基因敲入模型。 波士顿儿童医院Luigi Notarangelo。 项目＃4严重合并免疫缺陷的小鼠模型。 波士顿儿童医院弗雷德·阿尔特（Fred Alt）。 核心行政核心 考克斯·特霍斯特（Cox Terhorst），贝丝以色列执事医疗中心。 拟议的研究的结果应导致对复杂且经常交替的更好理解 由单个基因突变引起的疾病表现。这些研究的结果应该 建议可以应用于这些PID患者的治疗策略，并可能揭示分子和 通常涉及免疫失调，自身免疫和癌症的细胞机制。