Pathophysiology of HTLV-I and HTLV-II Infection

描述(申请人提供)：尽管全球估计有100万例人类T淋巴细胞病毒(HTLV-I)感染病例，美国有超过19.7万例HTLV-II感染病例，但HTLV-I和HTLV-II感染的临床结果和发病机制仍未明确。这项HTLV预后研究(HOST)上一次资助期的数据表明，HTLV-II易患肺炎、支气管炎和关节炎，导致类似HTLV-I相关性脊髓病(HAM)的脊髓病，并与全因死亡率增加有关。HTLV-I此前曾与成人T细胞白血病(ATL)、HAM和关节炎、葡萄膜炎和虹膜炎有关。这些肺、神经和免疫综合征的临床或生物学特征还不是很好，尤其是HTLV-II。这个竞争性的延续项目将检验以下假设：1.感染HTLV-II，以及在较小程度上感染HTLV-I，由于HTLV诱导的免疫介导的肺损伤，容易发生肺炎和支气管炎。2.HTLV-II引起类似HTLV-I相关性脊髓病(HAM)的机制与免疫介导的神经毒性相似。3.HTLV-II，可能还有HTLV-I，与死亡率增加有关，这可能是由于恶性肿瘤和/或心血管原因导致的死亡率较高。4.HTLV-I和HTLV-II与关节炎和其他自身免疫性疾病的发病率较高相关。我们将在对1990-92年登记的154名HTLVI、387名HTLV-II和799名血清阴性的既往献血者的宿主队列的进一步前瞻性调查中检验这些假设。该小组迄今已完成6次两年一次的访问。这项申请建议从2005年到2009年增加2次就诊，包括有组织的健康访谈、筛查体检、病历审查和有针对性的医生诊断检查。将采集所有受试者的血液，以及疾病亚群的支气管肺泡灌洗液和脑脊液，用于HTLV病毒学和免疫学研究。

DESCRIPTION (provided by applicant): Despite an estimated 1 million case of human T-lymphotropic virus type I (HTLV-I) infection worldwide, and over 197,000 cases of infection with HTLV-II in the United States, the clinical outcomes and pathogenesis of HTLV-I and -II infection are still not well defined. Data from the previous funding period of this HTLV Outcomes Study (HOST) indicate that HTLV-II predisposes to pneumonia, bronchitis and arthritis, causes a myelopathy similar to HTLV-I associated myelopathy (HAM), and is associated with increased all-cause mortality. HTLV-I has previously been associated with adult T-cell leukemia (ATL), HAM and arthritis, uveitis and iritis. These pulmonary, neurologic and immunologic syndromes have not been well characterized clinically or biologically, especially for HTLV-II. This Competing Continuation Project will test the following hypotheses: 1. Infection with HTLV-II, and to a lesser degree HTLV-I, predisposes to pneumonia and bronchitis because of HTLV-induced, immune-mediated pulmonary damage. 2. HTLV-II causes myelopathy resembling HTLV-I associated myelopathy (HAM) via similar mechanisms immune-mediated neurotoxicity. 3. HTLV-II, and perhaps HTLV-I, is associated with increased mortality, perhaps due to a higher death rate from malignant and/or cardiovascular causes. 4. HTLV-I and -II are associated with a higher incidence of arthritis and other autoimmune conditions. We shall test these hypotheses during additional prospective investigation of the HOST cohort of 154 HTLVI, 387 HTLV-II and 799 stratum matched seronegative former blood donors enrolled in 1990-92. 6 biennial visits of this cohort have been completed to date. This application proposes 2 additional visits from 2005 through 2009, including structured health interviews, screening physical examinations, medical record review and targeted physician diagnostic work-ups. Blood will be collected from all subjects, and bronchoalveolar lavage fluid and cerebrospinal fluid from subsets with disease, for studies of HTLV virology and immunology.