Immunological Response and Disease Expression in HTLV-1

HTLV-1 的免疫反应和疾病表达

• 批准号: 6809773
• 负责人: Edgar M Carvalho
• 金额: $ 5.4万
• 依托单位: FEDERAL UNIVERSITY OF BAHIA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6809773
• 关键词: T lymphocyte; cell proliferation; cerebrospinal fluid; clinical research; enzyme linked immunosorbent assay; gene expression; human T cell leukemia; human T cell lymphotropic virus type 1; human subject; immune response; interferon gamma; magnetic resonance imaging

DESCRIPTION (provided by applicant): HTLV-1 infection cause abnormalities in the immunological response characterized by spontaneous T cell proliferation and production of high levels of pro-inflammatory (IFN-gamma and TNF-alpha) cytokines. The myelopathy associated to HTLV-1 (HAM/TSP) and acute T cell leukemia are the most important diseases related to HTLV-1 and the pathogenesis of these diseases are associated with abnormalities in the T cell response. However while abnormalities in T cell responses are found in a large percentage of individuals infected with HTLV-1, HAM/TSP is documented in less than 5% of the infected individuals. The major hypothesis of this application is that clinical, neurological and immunological abnormalities occur in higher frequency than previously described in HTLV-1 infected patients. The major aim of this application is to identify early, clinical and immunological markers of disease in HTLV-1 infected individuals. The aim 1 is to identify clinical manifestations associated to HTLV-I. This will be performed analyzing the clinical data that has been generated in the last 5 years and compared with blood donors not infected with HTLV-1 in a case control study. The aim 2 will determine by sophisticated complementary exams if HTLV-1 carriers who have immunological abnormalities similar to that observed in HAM/TSP will have early evidence of neurological involvement. This will be tested in a case control study comparing the neurological findings, cytokine levels in cerebral spinal fluid and magnetic resonance imaging in HTLV-1 carriers who have high levels of IFN-gamma and lack of modulation of IFN-gamma production, similar to that observed in HAM/TSP, with HTLV-1 carriers who have no or mild alterations in their immunological responses. Results of these studies will contribute to identify clinical and neurological manifestations associated with HTLV-1, which can be confirmed in the future by a longitudinal study in the natural history of disease and will shed light on future more effective and earlier therapeutic interventions to this disease.

描述（由申请人提供）：HTLV-1感染引起免疫应答异常，其特征在于自发性T细胞增殖和高水平促炎性（IFN-γ和TNF-α）细胞因子的产生。与HTLV-1相关的脊髓病（HAM/TSP）和急性T细胞白血病是与HTLV-1相关的最重要的疾病，并且这些疾病的发病机制与T细胞应答的异常相关。然而，虽然在大比例的HTLV-1感染个体中发现T细胞应答异常，但在不到5%的感染个体中记录了HAM/TSP。本申请的主要假设是临床、神经学和免疫学异常的发生频率高于先前在HTLV-1感染患者中描述的频率。本申请的主要目的是鉴定HTLV-1感染个体中疾病的早期、临床和免疫学标志物。目的1是确定与HTLV-I相关的临床表现。这将通过分析过去5年中生成的临床数据进行，并与病例对照研究中未感染HTLV-1的献血者进行比较。目标2将通过复杂的补充检查来确定具有类似于HAM/TSP中观察到的免疫异常的HTLV-1携带者是否具有神经系统受累的早期证据。这将在一项病例对照研究中进行测试，该研究比较了具有高水平IFN-γ且缺乏IFN-γ产生调节的HTLV-1携带者与免疫应答无改变或轻度改变的HTLV-1携带者的神经学结果、脑脊液中的细胞因子水平和磁共振成像，该研究与HAM/TSP中观察到的结果相似。这些研究的结果将有助于确定与HTLV-1相关的临床和神经学表现，这可以在未来通过疾病自然史的纵向研究得到证实，并将阐明未来对这种疾病更有效和更早的治疗干预。