PATHOPHYSIOLOGY OF HTLV1 AND HTLVII INFECTION

尽管全世界估计有100万例人类t淋巴细胞嗜型病毒（HTLV-I）感染，在美国有超过17.4万例HTLV-II感染，但HTLV-I和-II感染的临床结果和发病机制尚不明确。来自nhlbi赞助的逆转录病毒流行病学捐赠者研究（REDS） HTLV队列研究的最新数据和文献表明，HTLV- ii易患其他传染病，并可能导致类似HTLV- i相关脊髓病（HAM）的脊髓病。htlv - 1也可引起成人t细胞白血病（ATL），但它是否会增加其他恶性肿瘤的发病率尚存争议。最后，有报道称HTLV-I和/或HTLV-II与免疫综合征相关，包括关节炎、葡萄膜炎和虹膜炎；然而，这些关联尚未得到证实。本项目将检验以下从文献和我们自己的初步数据中得出的假设：HTLV-II和HTLV-I的感染程度较低，易患其他传染病。2. HTLV-II引起的脊髓病与HTLV-I相关的脊髓病（HAM）相似。3. HTLV-I与ATL和其他恶性肿瘤的风险增加有关。4. 自身免疫性疾病（如关节炎和葡萄膜炎）在HTLV-I和-II感染者中更为常见。我们将在对1990- 1992年登记的154名HTLV-I、387名HTLV-II和799名血清阴性前献血者的red队列进行额外的前瞻性调查中检验这些假设。到1998年为止，在国家卫生和社会福利部初步红皮书合同的资助下，将完成对这一群体的四次后续访问。这项申请提议从1999年至2004年再进行两次两年一次的访问，包括有组织的健康面谈、选定的体检、医疗记录审查和有针对性的诊断检查。每次访视时将采集所有受试者的血液，用于全血细胞计数、HTLV病毒载量测量和广泛的标本库。

Despite an estimated 1 million cases of human T-lymphotropic virus type I (HTLV-I) infection worldwide, and over 174,000 cases of infection with HTLV-II in the United States, the clinical outcomes and pathogenesis of HTLV-I and -II infection are not well defined. Recent data from the NHLBI-sponsored Retrovirus Epidemiology Donor Study (REDS) HTLV Cohort Study and the literature suggest that HTLV-II predisposes to other infectious disease, and that it may cause a myelopathy similar to HTLV-I associated myelopathy (HAM). HTLV-I also causes adult T-cell leukemia (ATL), but it is controversial whether it increases the rate of other malignancies. Finally, there are reports that HTLV-I and/or HTLV-II are associated with immunologic syndromes including arthritis, uveitis and iritis; however, these associations have not been proven. This Project will test the following hypotheses derived from the literature and our own preliminary data: 1. Infection with HTLV-II, and to a lesser degree HTLV-I, predisposes to other infectious diseases. 2. HTLV-II causes myelopathy similar to HTLV-I associated myelopathy (HAM). 3. HTLV-I is associated with an increased risk of ATL and other malignancies. 4. Autoimmune conditions (e.g. arthritis and uveitis) are more common among HTLV-I and -II infected persons. We shall test these hypotheses during additional prospective investigation of the REDS cohort of 154 HTLV-I, 387 HTLV-II and 799 stratum matched seronegative former blood donors enrolled in 1990-92. Four follow-up visits of this cohort will have been completed through 1998 under funding by the initial NHLBI REDS contracts. This application proposes two additional biennial visits from 1999 through 2004, including structured health interviews, selected physical examinations, medical record review and targeted diagnostic work-ups. Blood will be collected from all subjects at each visit for complete blood counts, measurement of HTLV viral load, and for an extensive specimen repository.