Rosenblatt J D, Tomkins P, Rosenthal M, Kacena A, Chan G, Valderama R, Harrington W, Saxton E, Diagne A, Zhao J Q
Department of Medicine, UCLA School of Medicine.
AIDS. 1992 Oct;6(10):1151-8. doi: 10.1097/00002030-199210000-00014.
Human T-cell leukemia virus types I (HTLV-I) and II (HTLV-II) are closely related human retroviruses. HTLV-I has been implicated in a chronic progressive myelopathy, known as tropical spastic paraparesis (TSP) or HTLV-I-associated myelopathy (HAM). We sought to determine whether autoantibodies to brain antigens were present in the cerebrospinal fluid (CSF) of a patient with chronic progressive spastic myelopathy with evidence of both HIV-1 infection and HTLV-I/II seropositivity.
A 54-year-old bisexual man with clinical features of HAM/TSP of over 20 years' duration was followed.
We applied discriminatory DNA amplification (polymerase chain reaction) to distinguish HTLV-I from HTLV-II and to verify co-infection with HIV-1. The patient's CSF was used to screen a human brain cDNA expression library to identify antibodies directed against brain antigens. Autoreactive bacteriophage clones were isolated and sequenced.
The patient was found to be co-infected with both HIV-1 and HTLV-II, but not with HTLV-I. HTLV-II proviral levels in the peripheral blood remained relatively constant, despite therapy with zidovudine. Prominent oligoclonal banding of immunoglobulins was present in the patient's CSF. A single repeatedly reactive cDNA clone was identified, by screening with CSF antibody, sequenced, and found to be the human homologue of the rat insulinoma gene, rig.
HTLV-II infection may predispose to development of a HAM/TSP-like illness. Autoimmune mechanisms, such as autoantibody formation, may play a role in pathogenesis.
人类I型和II型嗜T细胞病毒(HTLV-I和HTLV-II)是密切相关的人类逆转录病毒。HTLV-I与一种慢性进行性脊髓病有关,即热带痉挛性截瘫(TSP)或HTLV-I相关脊髓病(HAM)。我们试图确定在一名患有慢性进行性痉挛性脊髓病且有HIV-1感染和HTLV-I/II血清学阳性证据的患者的脑脊液(CSF)中是否存在针对脑抗原的自身抗体。
对一名患有超过20年HAM/TSP临床特征的54岁双性恋男性进行随访。
我们应用鉴别性DNA扩增(聚合酶链反应)来区分HTLV-I和HTLV-II,并验证与HIV-1的合并感染。患者的脑脊液用于筛选人脑cDNA表达文库,以鉴定针对脑抗原的抗体。分离并测序自身反应性噬菌体克隆。
发现该患者同时感染了HIV-1和HTLV-II,但未感染HTLV-I。尽管接受了齐多夫定治疗,外周血中HTLV-II前病毒水平仍保持相对稳定。患者的脑脊液中存在明显的免疫球蛋白寡克隆带。通过用脑脊液抗体筛选,鉴定出一个单一的反复反应性cDNA克隆,进行测序后发现它是大鼠胰岛素瘤基因rig的人类同源物。
HTLV-II感染可能易导致类似HAM/TSP疾病的发生。自身免疫机制,如自身抗体形成,可能在发病机制中起作用。