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

Biomarkers of spontaneous acute hepatitis C virus resolution

自发性急性丙型肝炎病毒消退的生物标志物

基本信息

批准号：
8458955
负责人：
Suganya Selvarajah
金额：
$ 11.28万
依托单位：
VITALANT
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-04-15 至 2015-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8458955
关键词：
Acute Acute Hepatitis C Applications Grants Biological Markers Biology Blood Transfusion CXCL10 gene Chronic Chronic Hepatitis C Clinical Clinical Management Cohort Studies Data Disease Outcome Genetic Genetic Polymorphism Hepatitis C Hepatitis C Transmission Hepatitis C virus Immune Immunologic Factors Individual Infection Interleukin-10 Interleukin-18 Kinetics Mediating National Heart, Lung, and Blood Institute Outcome Outcomes Research Patients Phase Play Prevention Public Health RNA Reporting Research Research Proposals Resolution Risk Role Sampling Serum Single Nucleotide Polymorphism Specimen Study Subject TNF gene Testing Time Transfusion Transfusion-Transmitted Virus Viral Viral Load result Viremia Virus base biobank chemokine cohort combat cytokine design follow-up improved novel outcome forecast protein expression repository sample collection transmission process

项目摘要

DESCRIPTION (provided by applicant): In the proposed study we will investigate soluble immunologic factors present in serum following transfusion transmission through the course of acute HCV infection to identify biomarkers influencing and predicting spontaneous HCV clearance versus chronic HCV infection. TTVS is a rare cohort with a large number of serial serum samples spanning a year following acute HCV infection with well characterized clinical parameters including clear categorization of disease outcome status. These samples and predicate data will allow us to effectively examine the specific aims outlined below. The proposed research will demonstrate the importance of donor and recipient sample collection and retention. The research will also show how the ongoing use of biorepositories created and maintained by NHLBI can afford continuing value by improving our understanding of Hepatitis C virus biology greater than thirty years after the TTVS repository was developed. We have generated preliminary results from sixteen TTVS subjects and observed changes in expression kinetics of IP- 10, TNF-? and IL-10 during acute HCV infection in both HCV resolvers and chronic HCV infections, albeit different expression kinetics in the two groups. We observed elevation in soluble IL-2Ra expression only in spontaneous HCV resolvers compared to chronic HCV or uninfected controls. In Specific Aim1, we will determine IP-10, TNF-??, IL-10, sIL-2Ra and TGF-?? expression kinetics in sera during acute HCV infection following transfusion transmission in the full cohort of 94 infected TTVS recipients. In Specific Aim 2, we will determine IL-18 and/or IL-28B protein expression as a biomarker of spontaneous HCV resolution in transfusion transmitted HCV infection. Based on recent groundbreaking findings, we will also determine whether IL-18 and IL-28B genetic polymorphisms correlate with spontaneous HCV resolution in the TTVS cohort. Given the extent of individual suffering and the overall impact to public health as a result of HCV infection, there is a high priority for continue research into HCV prevention, prognosis and clinical management. The examination of immune correlates with clinical outcome in a cohort of Acute Hepatitis C virus infection such as TTVS will advance our capacity to combat and treat HCV.

描述（由申请方提供）：在拟定的研究中，我们将研究急性HCV感染过程中输血传播后血清中存在的可溶性免疫因子，以确定影响和预测HCV自发清除与慢性HCV感染的生物标志物。TTVS是一个罕见的队列，在急性HCV感染后一年内有大量的连续血清样本，具有良好的临床特征参数，包括疾病结局状态的明确分类。这些样本和同品种器械数据将使我们能够有效地检查下述特定目标。拟议的研究将证明供体和受体样本收集和保留的重要性。该研究还将展示NHLBI创建和维护的生物储存库的持续使用如何通过提高我们对TTVS储存库开发后30多年的丙型肝炎病毒生物学的理解来提供持续价值。我们已经产生了初步的结果，从16 TTVS科目和观察IP- 10，TNF-？和IL-10在急性HCV感染期间在HCV消退者和慢性HCV感染中，尽管两组中的表达动力学不同。与慢性HCV或未感染对照组相比，我们观察到可溶性IL-2 Ra表达仅在自发性HCV消退者中升高。在特定目标1中，我们将测定IP-10、TNF-？？、IL-10、sIL-2 Ra和TGF-β 1的表达。在94名感染TTVS受者的整个队列中，输血传播后急性HCV感染期间血清中的表达动力学。在具体目标2中，我们将确定IL-18和/或IL-28 B蛋白表达作为输血传播HCV感染中HCV自发消退的生物标志物。基于最近的突破性发现，我们还将确定IL-18和IL-28 B基因多态性是否与TTVS队列中的自发HCV消退相关。鉴于HCV感染对个人痛苦的程度和对公共卫生的总体影响，继续研究HCV预防、预后和临床管理是一个高度优先事项。在急性丙型肝炎病毒感染队列中，如TTVS，免疫相关性检查与临床结局相关，提高我们对抗和治疗HCV的能力。