CORE--CLINICAL LABORATORY CORE

该临床研究核心设施的目标是及早识别 DHF发生风险增加的免疫学和病毒学标志物 （项目1）。 该核心将测量患者免疫激活的血浆标志物 入组项目1研究：细胞因子水平，例如IL-1 β，TNF-α， IL-2、IL-6; T细胞活化产物水平，例如可溶性CD 8 （sCD 8）、可溶性CD 4（sCD 4）;以及休克和血浆 渗漏，例如血小板活化因子（PAF）和补体成分。 核心将评估选定患者的细胞免疫反应 入组项目1：T淋巴细胞标志物（如IL-2）的表达 受体，HLA DR;单核细胞/巨噬细胞活化，例如Fc上调 受体;和登革热特异性细胞毒性T淋巴细胞活性水平 在急性感染期间。（D和DHF）。 这个核心将量化 人单核细胞中的登革热病毒中和和增强抗体 比色法 该中心还将进行诊断和定量病毒学研究 对于项目1，例如在蚊子中分离登革热病毒， 免疫细胞化学检测登革抗原 急性病患者PBMC中的技术。 核心将分析I类和II类之间的相关性 组织相容性（HLA）类型与D vs. DHF。 核心还将评估长期的中和和增强 抗体和T细胞记忆的患者在项目1与D或DHF。 这些 结果将表征HLA相关的登革热免疫反应， 评估长期有益（中和）和有害（增强） 这些抗体对疫苗的开发很重要。 泰国的这个设施将处理、冷冻保存和运送病人 用于分子免疫学研究的项目1样本（血浆和PBMC） 在项目2（UMMC）和病毒株的分子表征， 项目3（YARU）。

The goal of this Clinical Research Core Facility is to identify early immunologic and virologic markers of increased risk of developing DHF (Project 1). This core will measure plasma markers of immune activation in patients enrolled in Project 1 studies: cytokine levels, e.g. IL-Ibeta, tnf-ALPHA, il-2, il-6; levels of products of T cell activation, e.g. soluble CD8 (sCD8), soluble CD4 (sCD4); and levels of mediators of shock and plasma leakage, e.g. platelet activating factor (PAF), and complement components. The core will assess cellular immune responses in selected patients enrolled in Project 1: expression of T lymphocyte markers e.g. IL-2 receptors, HLA DR; monocyte/macrophage activation e.g. upregulation of Fc receptors; and the level of dengue-specific cytotoxic T lymphocyte activity during acute infections. (D and DHF). This core will quantitate neutralizing and enhancing antibodies to dengue virus in a human monocyte assay. The core will also perform diagnostic and quantitative virologic studies for Project 1, e.g. dengue virus isolation in mosquitoes, measure dengue antibody responses and detect dengue antigens by immunocytochemical techniques in PBMC of acutely ill patients. The core will analyze correlations between Class I and Class II histocompatibility (HLA) types of patients enrolled in Project 1 with D vs. DHF. The core will also assess the long term neutralizing and enhancing antibodies and T cell memory in patients in Project 1 with D or DHF. These results will characterize HLA-associated immune responses to dengue, and assess long-term beneficial (neutralizing) and detrimental (enhancing) antibodies which are important for vaccine development. This facility in Thailand will process, cryopreserve and ship patient samples (plasma and PBMC) from Project #1 for molecular immunologic studies in Project 2 (UMMC) and molecular characterization of virus strains in Project 3 (YARU).