High Human T Cell Leukemia Virus Type-1 (HTLV-1) Provirus Load in Patients with HTLV-1 Carriers Complicated with HTLV-1-unrelated disorders
High Human T Cell Leukemia Virus Type-1 (HTLV-1) Provirus Load in Patients with HTLV-1 Carriers Complicated with HTLV-1-unrelated disorders
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DOI：
10.1186/1743-422x-7-81
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发表时间：
2010-04-28
期刊：
影响因子：
4.8
通讯作者：
Kamihira, Shimeru
中科院分区：
文献类型：
--
作者：
Sasaki, Daisuke;Doi, Yuko;Kamihira, Shimeru
背景资料：为了阐明HTLV-1前病毒载量（VL）高的临床和病毒学意义，我们采用聚合酶链反应（PCR）定量方法同时检测了无症状和有症状携带者的实际血液样本中的VL和克隆扩增状态（外周血单个核细胞的感染细胞%）和Southern印迹杂交（SBH）方法。本研究揭示了极高的VL与高密度涂片与或不寡克隆带在SBH。在总共33个样品中的16个（43.2%）中观察到10%或更高的高VL（13个无症状携带者中的一个，12个有症状携带者中的8个，以及8个患有淋巴瘤型ATL而没有循环ATL细胞的患者中的7个）。特别是，50%或更高的极高VL仅限于有症状的携带者，其条带发现总是包含至少来自HTLV-1感染的多克隆扩增细胞的致密涂片。连续样本显示，VL值与有无致密涂片同步，并在致密涂片消失的同时下降。致密涂片在基础疾病的活动期短暂出现。涂片消失后，几个克隆条带变得可见并持续保留，解释了HTLV-1感染细胞建立克隆性的过程。只有寡克隆条带的病例倾向于长时间维持在20%左右的稳定VL。两个这样的情况下开发ATL 4和3.5年后，表明高VL寡克隆带可能是一个诱发风险ATL。结论：极高VL的主要贡献者似乎是短暂出现的密集涂片检测的敏感性水平SBH，对应于多克隆扩增的HTLV-1感染的细胞，包括丰富的小克隆。密集涂片消失后保留的主要克隆稳定存在，并逐步获得各种恶性特征。
Background: To address the clinical and virological significance of a high HTLV-1 proviral load (VL) in practical blood samples from asymptomatic and symptomatic carriers, we simultaneously examined VL and clonal expansion status using polymerase chain reaction (PCR) quantification (infected cell % of peripheral mononuclear cells) and Southern blotting hybridization (SBH) methods.Results: The present study disclosed extremely high VL with highly dense smears with or without oligoclonal bands in SBH. A high VL of 10% or more was observed in 16 (43.2%) of a total of 33 samples (one of 13 asymptomatic carriers, 8 of 12 symptomatic carriers, and 7 of 8 patients with lymphoma-type ATL without circulating ATL cells). In particular, an extremely high VL of 50% or more was limited to symptomatic carriers whose band findings always contained at least dense smears derived from polyclonally expanded cells infected with HTLV-1. Sequential samples revealed that the VL value was synchronized with the presence or absence of dense smears, and declined at the same time as disappearing dense smears. Dense smears transiently emerged at the active stage of the underlying disease. After disappearance of the smears, several clonal bands became visible and were persistently retained, explaining the process by which the clonality of HTLV-1-infected cells is established. The cases with only oligoclonal bands tended to maintain a stable VL of around 20% for a long time. Two of such cases developed ATL 4 and 3.5 years later, suggesting that a high VL with oligoclonal bands may be a predisposing risk to ATL.Conclusion: The main contributor to extremely high VL seems to be transient emergence of dense smears detected by the sensitivity level of SBH, corresponding to polyclonal expansion of HTLV-1-infected cells including abundant small clones. Major clones retained after disappearance of dense smears stably persist and acquire various malignant characteristics step by step.