Biomarkers of spontaneous acute hepatitis C virus resolution

描述（由申请人提供）：在拟议的研究中，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是一个罕见的队列研究，在急性HCV感染后的一年内，有大量的连续血清样本，具有很好的临床参数特征，包括明确的疾病结局状态分类。这些样本和谓词数据将使我们能够有效地检查下面概述的具体目标。拟议的研究将证明供体和受体样本收集和保存的重要性。该研究还将表明，在TTVS储存库开发30多年后，NHLBI创建和维护的生物储存库的持续使用如何能够通过提高我们对丙型肝炎病毒生物学的理解来提供持续价值。我们已经从16名TTVS受试者中获得了初步结果，并观察到了IP- 10、TNF-？和IL-10在急性HCV感染者和慢性HCV感染者中的表达动力学不同。与慢性HCV或未感染的对照组相比，我们观察到仅在自发性HCV消退者中可溶性IL-2Ra表达升高。在Specific Aim1中，我们将测定IP-10、TNF-?？、IL-10、sIL-2Ra和TGF-?？输血传播后急性丙型肝炎病毒感染的血清表达动力学（94例TTVS感染者）在特异性目标2中，我们将确定IL-18和/或IL-28B蛋白表达作为输血传播性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-28B遗传多态性是否与TTVS队列中自发HCV消退相关。鉴于丙型肝炎病毒感染给个人造成的痛苦程度和对公共卫生的总体影响，继续研究丙型肝炎病毒的预防、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（如TTVS）队列中，免疫检查与临床结果相关

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.