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:8262303
- 负责人:
- 金额:$ 11.85万
- 依托单位:
- 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 2014-03-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAcute Hepatitis CApplications GrantsBiological MarkersBiologyBlood TransfusionCXCL10 geneChronicChronic Hepatitis CClinicalClinical ManagementCohort StudiesDataDisease OutcomeGeneticGenetic PolymorphismHepatitis CHepatitis C TransmissionHepatitis C virusImmuneImmunologic FactorsIndividualInfectionInterleukin-10Interleukin-18KineticsMediatingNational Heart, Lung, and Blood InstituteOutcomeOutcomes ResearchPatientsPhasePlayPreventionPublic HealthRNAReportingResearchResearch ProposalsResolutionRiskRoleSamplingSerumSingle Nucleotide PolymorphismSpecimenStudy SubjectTNF geneTestingTimeTransfusionTransfusion-Transmitted VirusViralViral Load resultViremiaVirusbasebiobankchemokinecohortcombatcytokinedesignfollow-upimprovednoveloutcome forecastprotein expressionrepositorysample collectiontransmission 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(申请人提供):在拟议的研究中,我们将调查急性丙型肝炎病毒感染过程中输血传播后血清中存在的可溶性免疫学因素,以确定影响和预测丙型肝炎病毒自发清除与慢性丙型肝炎病毒感染的生物标志物。TTVS是一个罕见的队列,在急性丙型肝炎感染后一年内有大量连续的血清样本,具有良好的临床参数,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。拟议的研究将证明捐赠者和接受者样本收集和保留的重要性。这项研究还将展示在TTVS储存库开发30多年后,如何通过提高我们对丙型肝炎病毒生物学的理解,使NHLBI创建和维护的生物储存库的持续使用具有持续的价值。我们已经产生了16个TTV受试者的初步结果,并观察到IP-10、TNF-?的表达动力学变化。和IL-10在急性丙型肝炎病毒感染和慢性丙型肝炎病毒感染中的表达,尽管在两组中表达动力学不同。我们观察到只有自发的丙型肝炎病毒解决者与慢性丙型肝炎病毒感染者或未感染的对照组相比,可溶性IL-2ra的表达增加。在特定的Aim1中,我们将测定IP-10、TNF-β、IL-10、sIL-2ra和转化生长因子-β。94例TTV感染者输血传播后急性丙型肝炎病毒在血清中的表达动态。在特定目标2中,我们将确定IL-18和/或IL-28B蛋白的表达作为输血传播的丙型肝炎病毒感染患者自发丙型肝炎病毒消退的生物标志物。基于最近的开创性发现,我们还将确定IL-18和IL-28B基因多态是否与TTV队列中的自发丙型肝炎病毒溶解相关。鉴于丙型肝炎病毒感染对个人的痛苦程度和对公众健康的整体影响,继续研究丙型肝炎病毒的预防、预后和临床管理是高度优先的。在TTV等急性丙型肝炎病毒感染队列中,免疫检查与临床转归相关
提高我们抗击和治疗丙型肝炎的能力。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('Suganya Selvarajah', 18)}}的其他基金
Immunotherapeutic for ATTR/AL Cardiac Amyloidosis
ATTR/AL 心脏淀粉样变性的免疫治疗
- 批准号:
10081324 - 财政年份:2020
- 资助金额:
$ 11.85万 - 项目类别:
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
- 批准号:
8458955 - 财政年份:2012
- 资助金额:
$ 11.85万 - 项目类别:
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