CMV Immune Response & Long-Term Outcome of CMV Retinitis

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，并可以告知临床医生何时开始、停止或重新进行抗CMV治疗是最佳的，以防止有或已经诊断为这种机会性感染的艾滋病患者发生和进展性CMV视网膜炎（CMVR），从而防止他们未来的视力丧失。这项工作将研究CD8+ T淋巴细胞IFNg反应（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结果的假设。具体来说，主要目的是通过流式细胞术比较cmv刺激的CD8+/IFNg+ T淋巴细胞反应，这些反应来自美国国家眼科研究所赞助的艾滋病眼部并发症多中心纵向研究（LSOCA）中储存的PBMC样本，这些样本来自CMVR事件或进展事件之前的病例组和匹配的对照LSOCA受试者组，他们在研究中没有后续事件或进展性CMVR事件。主要的次要目的是确定额外的临床特征（使用HAART，使用抗CMV治疗），标准的临床实验室测量（血浆HIV RNA，血红蛋白）或CMV病毒血症测量（通过血浆CMV DNA）是否会增强测量CMV抗原特异性CD8+/IFNg+ T淋巴细胞反应对事件或进展CMVR的预测价值。拟议的工作将采用观察性病例对照研究设计。研究人群将包括已经在LSOCA注册的受试者，目前的中位随访时间为2年。作为LSOCA协议的一部分，收集了广泛的临床数据，并将其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标本在所有lsoca授权的研究访问中获得，并储存在中央储存库中。拟议的工作包括cmv抗原特异性免疫测定检测已经获得并作为LSOCA方案的一部分存储的PBMC标本，然后分析免疫测定结果与已经作为LSOCA方案的一部分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。

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.