Core B: Immunoassay Core

核心 B：免疫测定核心

基本信息

批准号：
10188601
负责人：
SOTIRIOS TSIMIKAS
金额：
$ 11.28万
依托单位：
LA JOLLA INSTITUTE FOR IMMUNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-01 至 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10188601
关键词：
Anti-Idiotypic Antibodies Antibodies Antigen-Antibody Complex Apolipoproteins B Arterial Fatty Streak Arteries Atherosclerosis Autoantibodies B-Lymphocytes Biological Biological Assay Biological Markers Biological Phenomena Biology Blood specimen CD4 Positive T Lymphocytes Cardiovascular system Cell Communication Cell physiology Cholesterol Esters Clinical Clinical Data Data Doctor of Philosophy Epitopes Event High Density Lipoproteins Human Immune Immunoassay Immunoglobulin G Immunoglobulin M Individual Inflammation Knowledge Laboratories Lipoprotein (a)Lipoproteins Lymphocyte Measurement Measures Mus Natural Immunity Nature Oxides Patients Phospholipids Plasma Principal Investigator Procedures Publishing Research Personnel Research Proposals Services Specimen T-Lymphocyte Testing Work atherogenesis atheroprotective cardiovascular disorder risk coronary artery calcium cytokine experimental study improved monocyte mouse model murine monoclonal antibody natural antibodies oxidation response

项目摘要

Core B Project Summary Core B will work with each of the four projects to provide relevant immunoassays in mice and in humans: Project 1 with Dr Hedrick will use mouse models to test the impact of new monocyte subsets that regulate T and B cell responses in the artery wall, on atherogenesis and innate immunity. The Core will be able to measure IgG and IgM autoantibodies to oxidation-specific epitopes (OSE) and ApoB-immune complexes, as well as total IgG and IgM plasma levels to assess the impact of these monocyte subsets and interaction with lymphocytes on these measurements. These can then be analyzed according to B1 and B2 cell function from Dr. McNamara's projects and to also correlate with monocyte cytokine release from Dr. Ley's experiments. Project 2 with Dr. Miller will use the Core to measure oxidized cholesteryl esters on individual lipoproteins, an assay that has been co-developed by our laboratory with Dr. Miller and for which preliminary clinical data is provided in his section. Clinical assays that we have established, such as OxPL-apoB, Lp(a), and IgG and IgM autoantibodies and ApoB-immune complexes will also be measured. These measures can then be related to both the presence and extent of coronary artery calcium (CAC), as well as the progression of CAC and the relationship with cardiovascular events. Furthermore, they can be correlated with AIBP levels and HDL parameters from the various experiments. Project 3 with Dr McNamara will evaluate the mechanism that regulates their ability to produce atheroprotective moieties such as IgM to OSE. This project is expected to generate significant data in B1 biology in mouse models, all of which will be highly relevant to measuring IgG and IgM autoantibody titers. We also have the ability to measure the presence of the atheroprotective antibody E06 in such mice as we have access to an anti-idiotype antibody to E06, AB1-2. Finally, measuring total levels of IgG and IgM antibodies is an important aspect in interpreting experimental studies, which will also be measured. Such assays are currently available and have been previously described and published in collaborative work with Dr. McNamara Project 4 with Dr. Ley will define the size and nature of the ApoB-specific CD4 T cell in mice. The mouse apoB-immune complex assays capture murine apoB using murine monoclonal antibody antibody LF3 and then assess the presence of a bound antibody to the apoB. These assays will be highly relevant to this work in interpreting whether immune complexes containing murine apoB are generated in these mice. Furthermore, we can measure murine total apoB levels with these assays as a control measure.

核心B项目总结 Core B 将与四个项目中的每一个项目合作，在小鼠和人类中提供相关的免疫测定： Hedrick 博士的项目 1 将使用小鼠模型来测试新单核细胞亚群的影响，这些亚群调节动脉壁中 T 细胞和 B 细胞对动脉粥样硬化形成和先天免疫的反应。核心将能够测量针对氧化特异性表位 (OSE) 和 ApoB 免疫复合物的 IgG 和 IgM 自身抗体，如以及总 IgG 和 IgM 血浆水平，以评估这些单核细胞亚群的影响以及与淋巴细胞对这些测量结果的影响。然后可以根据 B1 和 B2 细胞功能对这些进行分析 McNamara 博士的项目，也与 Ley 博士实验中的单核细胞细胞因子释放相关。 Miller 博士的项目 2 将使用 Core 测量个体的氧化胆固醇酯脂蛋白，这是我们实验室与米勒博士共同开发的一种检测方法，并为此进行了初步的研究他的部分提供了临床数据。我们已经建立的临床检测，例如 OxPL-apoB、Lp(a)、还将测量 IgG 和 IgM 自身抗体以及 ApoB 免疫复合物。这些措施可以然后与冠状动脉钙化（CAC）的存在和程度以及冠状动脉钙化的进展有关 CAC 与心血管事件的关系。此外，它们可以与 AIBP 水平相关来自各种实验的 HDL 参数。麦克纳马拉博士的项目 3 将评估调节其生产能力的机制动脉粥样硬化保护部分，例如 IgM 至 OSE。该项目预计将在 B1 中产生重要数据小鼠模型中的生物学，所有这些都与测量 IgG 和 IgM 自身抗体滴度高度相关。我们也有能力测量我们所拥有的小鼠中动脉粥样硬化抗体 E06 的存在获得 E06、AB1-2 的抗独特型抗体。最后，测量 IgG 和 IgM 抗体的总水平解释实验研究的一个重要方面，也将被测量。此类测定是目前可用，并且之前已与 McNamara 博士合作描述和发表 Ley 博士的项目 4 将确定小鼠体内 ApoB 特异性 CD4 T 细胞的大小和性质。这小鼠 apoB-免疫复合物检测使用鼠单克隆抗体抗体 LF3 捕获鼠 apoB 然后评估是否存在与 apoB 结合的抗体。这些测定将与此高度相关致力于解释这些小鼠中是否产生含有鼠 apoB 的免疫复合物。此外，我们可以用这些测定法测量小鼠总 apoB 水平作为对照测量。