CMV Immune Response & Long-Term Outcome of CMV Retinitis

巨细胞病毒免疫反应

• 批准号: 6848025
• 负责人: MARK A JACOBSON
• 金额: $ 25.92万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-02-01 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6848025
• 关键词: AIDS therapy; cytomegalovirus; cytomegalovirus retinitis; cytotoxic T lymphocyte; flow cytometry; helper T lymphocyte; human tissue; immune response; immunologic assay /test; interferon gamma; leukocyte activation /transformation; microorganism disease chemotherapy; outcomes research; polymerase chain reaction; prognosis; virus load

DESCRIPTION (provided by applicant): The aim of this proposal is to test the potential clinical utility of a CMV-specific immunoassay that correlates with protective CMV-specific immune responses and which could inform clinicians when it is optimal to initiate, discontinue or re-institute anti-CMV therapy in order to prevent incident and progressive CMV retinitis (CMVR) in AIDS patients at risk for or already diagnosed with this opportunistic infection and thus prevent their future vision loss. The proposed work will investigate the hypothesis that CD8+ T lymphocyte IFNg responses (measured by flow cytometry after stimulation with short, overlapping peptides of the CMV pp65 and IE proteins, as well as with whole CMV lysate) will accurately predict clinical CMVR outcomes. Specifically, the primary objective is to compare CMV-stimulated CD8+/IFNg+ T lymphocyte responses by flow cytometry in stored PBMC samples obtained in the National Eye Institute-sponsored multi-center Longitudinal Study of the Ocular Complications of AIDS (LSOCA) from groups of cases prior to CMVR incident or progression events and from groups of matched control LSOCA subjects who had no subsequent incident or progressive CMVR event on study. The main secondary objective is to determine if additional clinical characteristics (use of HAART, use of anti-CMV therapy), standard clinical laboratory measurements (plasma HIV RNA, hemoglobin) or measurement of CMV viremia (by plasma CMV DNA) will enhance the predictive value of measuring CMV antigen-specific CD8+/IFNg+ T lymphocyte responses for incident or progressive CMVR. The proposed work will employ an observational, case-control study design. The study population will consist of subjects who have already been enrolled in LSOCA and currently have a median 2 years of follow-up. Extensive clinical data are collected as part of the LSOCA protocol and entered into a central database managed at the SOCA Coordinating Center at Johns Hopkins School of Public Health. PMBC specimens are obtained at all LSOCA-mandated study visits and banked in a central repository. The proposed work involves CMV-antigen specific immunoassay testing of stored PBMC specimens that have already been obtained and stored as part of the LSOCA protocol and then analyzing the relationship of the immunoassay results to other clinical data already collected as part of the LSOCA protocol, including CMVR outcomes that are confirmed by central masked analysis of retinal photographs.

描述（由申请人提供）：本提案的目的是测试 CMV 特异性免疫测定的潜在临床效用，该免疫测定与保护性 CMV 特异性免疫反应相关，并且可以告知临床医生何时是启动、停止或重新启动的最佳时机。进行抗 CMV 治疗，以预防有感染风险或已诊断患有这种机会性感染的 AIDS 患者发生发生和进行性 CMV 视网膜炎 (CMVR)，从而防止他们未来视力丧失。拟议的工作将调查以下假设：CD8+ T 淋巴细胞 IFNg 反应（在用 CMV pp65 和 IE 蛋白的短重叠肽以及整个 CMV 裂解物刺激后通过流式细胞术测量）将准确预测临床 CMVR 结果。具体来说，主要目的是通过流式细胞术比较国家眼科研究所资助的艾滋病眼部并发症多中心纵向研究（LSOCA）中保存的 PBMC 样本中 CMV 刺激的 CD8+/IFNg+ T 淋巴细胞反应。在 CMVR 事件或进展事件之前以及来自研究中没有后续事件或进展 CMVR 事件的匹配对照 LSOCA 受试者组。主要次要目标是确定其他临床特征（使用 HAART、使用抗 CMV 治疗）、标准临床实验室测量（血浆 HIV RNA、血红蛋白）或 CMV 病毒血症测量（通过血浆 CMV DNA）是否会增强预测测量 CMV 抗原特异性 CD8+/IFNg+ T 淋巴细胞反应对于偶发或进行性 CMVR 的价值。拟议的工作将采用观察性病例对照研究设计。研究人群将包括已加入 LSOCA 且目前随访时间中位数为 2 年的受试者。作为 LSOCA 协议的一部分，收集了大量的临床数据，并输入约翰霍普金斯大学公共卫生学院 SOCA 协调中心管理的中央数据库。 PMBC 样本是在所有 LSOCA 授权的研究访问中获取的，并存储在中央存储库中。拟议的工作涉及对已作为 LSOCA 协议的一部分获得和存储的 PBMC 标本进行 CMV 抗原特异性免疫测定测试，然后分析免疫测定结果与作为 LSOCA 协议的一部分已收集的其他临床数据的关系，包括通过视网膜照片的中央掩模分析证实的 CMVR 结果。