Immunological Response and Disease Expression in HTLV-1

描述(由申请人提供)：HTLV-1感染导致免疫反应异常，特征是自发的T细胞增殖和产生高水平的促炎(干扰素-伽马和肿瘤坏死因子-α)细胞因子。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，这些疾病的发病与T细胞应答的异常有关。然而，尽管在很大比例的HTLV-1感染者中发现了T细胞反应的异常，但HAM/TSP在不到5%的感染者中被记录在案。这一应用的主要假设是，临床、神经和免疫异常发生的频率高于先前在HTLV-1感染患者中描述的频率。这项应用的主要目的是确定HTLV-1感染者的早期、临床和免疫学疾病标志物。目的1是确定与HTLV-I相关的临床表现。这将对过去5年产生的临床数据进行分析，并在病例对照研究中与未感染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观察到的免疫异常的HTLV-1携带者是否会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，比较HTLV-1携带者和HTLV-1携带者的神经学结果、脑脊液中细胞因子水平和磁共振成像，这些携带者的干扰素-γ水平较高，且缺乏干扰素-γ的产生调节，类似于在HAM/TSP中观察到的情况，而HTLV-1携带者的免疫反应没有或略有变化。这些研究的结果将有助于确定与HTLV-1相关的临床和神经表现，未来可以通过对疾病自然历史的纵向研究来证实这一点，并将有助于未来对这种疾病进行更有效和更早的治疗干预。

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.