Pathophysiology of HTLV-I and HTLV-II Infection

描述（由申请人提供）：尽管全球估计有100万例人嗜t淋巴病毒I型（HTLV-I）感染病例，在美国有超过19.7万例HTLV-II感染病例，但HTLV-I和-II感染的临床结果和发病机制仍然没有很好的定义。HTLV结局研究（HOST）先前资助期的数据表明，HTLV- ii易患肺炎、支气管炎和关节炎，导致类似HTLV- i相关脊髓病（HAM）的脊髓病，并与全因死亡率增加相关。HTLV-I先前与成人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、神经和免疫综合征还没有很好的临床或生物学特征，特别是HTLV-II。本竞赛延续项目将测试以下假设：HTLV-II和HTLV-I感染，由于htlv诱导的免疫介导的肺损伤，易患肺炎和支气管炎。2. HTLV-II通过相似的机制引起类似HTLV-I相关脊髓病（HAM）的脊髓病：免疫介导的神经毒性。3. HTLV-II和HTLV-I可能与死亡率增加有关，这可能是由于恶性和/或心血管原因导致的死亡率较高。4. HTLV-I和-II与关节炎和其他自身免疫性疾病的高发病率有关。我们将在对1990- 1992年登记的154例HTLVI、387例HTLV-II和799例地层匹配的血清阴性前献血者的HOST队列进行额外的前瞻性调查中检验这些假设。迄今为止，该队列已完成6次两年一次的访问。该申请建议从2005年到2009年再进行两次访问，包括结构化健康访谈、筛选体检、医疗记录审查和有针对性的医生诊断工作。将收集所有受试者的血液、支气管肺泡灌洗液和疾病亚群的脑脊液，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.