Lipka K, Tebbe B, Finckh U, Rolfs A
Neurochemical Research Laboratory, Free University of Berlin.
Clin Exp Dermatol. 1996 Jan;21(1):38-42.
The role of the human T-cell lymphotropic/leukaemia virus type I (HTLV-I) in the pathogenesis of autoimmune diseases of unknown cause, such as systemic lupus erythematosus (SLE), multiple sclerosis (MS) or Sjögren's syndrome (SS) has been discussed extensively. We have investigated whether SLE is in any way associated with exogenous HTLV-I. Using enzyme immunoassay (EIA), we found no seroreactivity against HTLV-I antigens in any of 24 SLE patients under investigation. Using a radioimmunoprecipitation assay (RIPA), there was also no expression of retroviral tax-protein demonstrable in 24 individuals with SLE. DNA preparations of peripheral blood cells, as well as isolated CD4- and CD8-positive cells, were examined for HTLV-I sequences (pol-, env-, gag-, LTR- and tax-region) using polymerase chain reaction (PCR). We were unable to demonstrate any specific HTLV-I PCR products in SLE specimens. Our data suggest that exogenous HTLV-I is not involved in the pathogenesis of SLE. Systemic lupus erythematosus (SLE) is a multisystem disease of unknown cause characterized by B-cell hyperactivity with hypergammaglobulinaemia and the formation of pathogenic autoantibodies. Patients may also show altered suppressor/helper T-cell ratios. Abnormalities in T-cell function include T-cell lymphopenia, expression of activation antigens and alteration of responses to mitogens and lymphokines. Human retroviruses are known to cause immune aberrations, such as diminished T-cell function and polyclonal B-cell stimulation, which are observed in patients with leukaemias, lymphomas and the acquired immunodeficiency syndrome (AIDS). Human T-cell lymphotropic/leukaemia (HTLV-I) is aetiologically linked with adult virus type I T-cell leukaemia (ATL) and tropical spastic paraparesis. A common feature of the HTLV family is an LTR encoded protein (tax protein, p40tax) which triggers viral protein production in the early stages of a retroviral infection. Detection of p40tax may indicate transcriptional activity of a provirus. Several investigators have examined the possible involvement of HTLV-I in SLE and have produced conflicting results, especially so far as seroreactivity against HTLV-I antigens is concerned. The discovery of HTLV-I like particles in murine lupus might also indicate an important role of exogenous viruses in SLE. Olsen and colleagues describe a high seropositivity to anti-HTLV-I- and anti-HTLV-III antibodies and evidence of viral replication in patients with SLE. Lin et al. also demonstrated anti-HTLV-I antibodies in SLE patients. However, other authors failed to detect anti-HTLV-I antibodies, proviral structures or viral transcripts in SLE. We investigated whether or not there are any indications of the presence of the exogenous retrovirus, HTLV-I, in patients with SLE, at immunological and genetic levels. We found neither immunological nor molecular biological evidence for the existence of HTLV-I in SLE patients. There were some weak suggestions of the presence of possibly endogenous retroviral sequences.
人类嗜T细胞病毒I型（HTLV-I）在诸如系统性红斑狼疮（SLE）、多发性硬化症（MS）或干燥综合征（SS）等病因不明的自身免疫性疾病发病机制中的作用已被广泛讨论。我们研究了SLE是否在任何方面与外源性HTLV-I有关。使用酶免疫测定（EIA），我们在所研究的24例SLE患者中均未发现针对HTLV-I抗原的血清反应性。使用放射免疫沉淀测定（RIPA），在24例SLE患者中也未检测到逆转录病毒tax蛋白的表达。使用聚合酶链反应（PCR）对外周血细胞以及分离的CD4和CD8阳性细胞的DNA制剂进行HTLV-I序列（pol-、env-、gag-、LTR-和tax区域）检测。我们在SLE标本中未能检测到任何特异性的HTLV-I PCR产物。我们的数据表明外源性HTLV-I不参与SLE的发病机制。系统性红斑狼疮（SLE）是一种病因不明的多系统疾病，其特征为B细胞功能亢进伴高球蛋白血症以及致病性自身抗体的形成。患者还可能表现出抑制性/辅助性T细胞比例改变。T细胞功能异常包括T细胞淋巴细胞减少、活化抗原的表达以及对有丝分裂原和淋巴因子反应的改变。已知人类逆转录病毒会导致免疫异常，如T细胞功能减退和多克隆B细胞刺激，这在白血病、淋巴瘤和获得性免疫缺陷综合征（AIDS）患者中可见。人类嗜T细胞病毒I型（HTLV-I）在病因上与成人T细胞白血病病毒I型（ATL）和热带痉挛性截瘫有关。HTLV家族的一个共同特征是一种LTR编码蛋白（tax蛋白，p40tax），它在逆转录病毒感染的早期阶段触发病毒蛋白的产生。检测p40tax可能表明前病毒的转录活性。几位研究者已研究了HTLV-I可能参与SLE的情况，并得出了相互矛盾的数据，尤其是就针对HTLV-I抗原的血清反应性而言。在小鼠狼疮中发现类HTLV-I颗粒也可能表明外源性病毒在SLE中起重要作用。奥尔森及其同事描述了SLE患者中抗HTLV-I和抗HTLV-III抗体的高血清阳性率以及病毒复制的证据。林等人也在SLE患者中检测到了抗HTLV-I抗体。然而，其他作者未能在SLE中检测到抗HTLV-I抗体、前病毒结构或病毒转录本。我们在免疫和基因水平上研究了SLE患者中是否有外源性逆转录病毒HTLV-I存在的迹象。我们未发现SLE患者中存在HTLV-I的免疫或分子生物学证据。有一些微弱迹象表明可能存在内源性逆转录病毒序列。
