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Long-term follow-up of HTLV-1 proviral load in asymptomatic carriers and in incident cases of HAM/TSP: what is its relevance as a prognostic marker for neurologic disease?成人T细胞白血病病毒1型（HTLV-1）无症状携带者和HAM/TSP新发病例的病毒前体负荷长期随访：其作为神经系统疾病预后标志物的相关性如何？
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本文引用的文献

1
An update on human T-cell leukemia virus type I (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) focusing on clinical and laboratory biomarkers.关于I型人类T细胞白血病病毒（HTLV-1）相关脊髓病/热带痉挛性截瘫（HAM/TSP）的最新进展，重点关注临床和实验室生物标志物。
Pharmacol Ther. 2021 Feb;218:107669. doi: 10.1016/j.pharmthera.2020.107669. Epub 2020 Aug 21.
2
Human T-lymphotropic virus type 1 (HTLV-1) and cellular immune response in HTLV-1-associated myelopathy/tropical spastic paraparesis.人类 T 淋巴细胞病毒 1 型（HTLV-1）与 HTLV-1 相关性脊髓病/热带痉挛性截瘫的细胞免疫应答。
J Neurovirol. 2020 Oct;26(5):652-663. doi: 10.1007/s13365-020-00881-w. Epub 2020 Jul 23.
3
Phylogenetic and phylodynamic study of Human T-cell lymphotropic virus Type 1 (HTLV-1) in Iran.伊朗人类 T 细胞嗜淋巴细胞病毒 1 型（HTLV-1）的系统发育和系统进化研究。
Infect Genet Evol. 2020 Nov;85:104426. doi: 10.1016/j.meegid.2020.104426. Epub 2020 Jun 16.
4
Complete sequence of human T cell leukemia virus type 1 in ATLL patients from Northeast Iran, Mashhad revealed a prematurely terminated protease and an elongated pX open reading frame III.在伊朗东北部马什哈德的 ATLL 患者中，完整的人类 T 细胞白血病病毒 1 序列揭示了一个过早终止的蛋白酶和一个伸长的 pX 开放阅读框 III。
Infect Genet Evol. 2019 Sep;73:460-469. doi: 10.1016/j.meegid.2019.05.012. Epub 2019 May 16.
5
HTLV-1: Regulating the Balance Between Proviral Latency and Reactivation.人类嗜T淋巴细胞病毒1型：调节前病毒潜伏与激活之间的平衡
Front Microbiol. 2018 Mar 19;9:449. doi: 10.3389/fmicb.2018.00449. eCollection 2018.
6
Evaluation of T Regulatory Lymphocytes Transcription Factors in HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) Patients.人嗜T淋巴细胞病毒1型相关脊髓病/热带痉挛性截瘫（HAM/TSP）患者中调节性T淋巴细胞转录因子的评估
Appl Biochem Biotechnol. 2017 Aug;182(4):1403-1414. doi: 10.1007/s12010-017-2406-7. Epub 2017 Jan 18.
7
Long-term follow-up of HTLV-1 proviral load in asymptomatic carriers and in incident cases of HAM/TSP: what is its relevance as a prognostic marker for neurologic disease?成人T细胞白血病病毒1型（HTLV-1）无症状携带者和HAM/TSP新发病例的病毒前体负荷长期随访：其作为神经系统疾病预后标志物的相关性如何？
J Neurovirol. 2017 Feb;23(1):125-133. doi: 10.1007/s13365-016-0484-x. Epub 2016 Sep 27.
8
Triple Therapy with Prednisolone, Pegylated Interferon and Sodium Valproate Improves Clinical Outcome and Reduces Human T-Cell Leukemia Virus Type 1 (HTLV-1) Proviral Load, Tax and HBZ mRNA Expression in Patients with HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis.泼尼松龙、聚乙二醇干扰素和丙戊酸钠三联疗法可改善人类T细胞白血病病毒1型（HTLV-1）相关脊髓病/热带痉挛性截瘫患者的临床结局，并降低HTLV-1前病毒载量、Tax和HBZ mRNA表达。
Neurotherapeutics. 2015 Oct;12(4):887-95. doi: 10.1007/s13311-015-0369-3.
9
Human T-lymphotropic Virus Type I (HTLV-I) Proviral Load and Clinical Features in Iranian HAM/TSP Patients: Comparison of HTLV-I Proviral Load in HAM/TSP Patients.伊朗HAM/TSP患者中I型人类嗜T淋巴细胞病毒（HTLV-I）前病毒载量及临床特征：HAM/TSP患者中HTLV-I前病毒载量的比较
Iran J Basic Med Sci. 2013 Mar;16(3):268-72.
10
Human T Lymphotropic Virus Type I (HTLV-I) Oncogenesis: Molecular Aspects of Virus and Host Interactions in Pathogenesis of Adult T cell Leukemia/Lymphoma (ATL).人类嗜T淋巴细胞病毒I型（HTLV-I）致癌作用：成人T细胞白血病/淋巴瘤（ATL）发病机制中病毒与宿主相互作用的分子层面
Iran J Basic Med Sci. 2013 Mar;16(3):179-95.

用于评估HAM/TSP患者临床结局的HTLV-1前病毒载量绝对定量逆转录-定量聚合酶链反应检测方法的开发

HTLV-1 Proviral Load Absolute RT-qPCR Development for Assessing on Clinical Outcomes in HAM/TSP Patients.

作者信息

Ariaee Nazila, Abbasnia Shadi, Sabet Faeze, Mirhossein Ali, Ahmadi Ghezeldasht Sanaz, Moshfegh Mehdi, Boostani Reza, Rezaee Seyed Abdolrahim

机构信息

The first and the second authors contributed equally to this work.

Immunology Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Rep Biochem Mol Biol. 2023 Oct;12(3):393-402. doi: 10.61186/rbmb.12.3.393.

DOI:10.61186/rbmb.12.3.393
PMID:38618262
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11015923/
Abstract

BACKGROUND

The significance of HTLV-1 proviral load as a prognostic biomarker in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) has been a subject of controversy. This study aims to assess the impact of HTLV-1 proviral load (PVL) on the clinical outcome in patients with HAM/TSP.

METHODS

An absolute quantitative HTLV-1 PVL RT-qPCR, TaqMan method was developed with 100% sensitivity and specificity. Then, from 2005-2018, the HTLV-1 PVL of 90 eligible newly diagnosed HAM/TSP patients were assessed for demographic, clinical symptoms and their associations with HTLV-1-PVL.

RESULTS

The quality control of the designed RT-qPCR showed a sensitivity and specificity of 100%. Spasticity in lower limbs in 58.9% and urinary symptoms in 17.8% of HAM/TSPs were observed. Using this designed RT-qPCR, the HTLV-1-PVL strongly affected spasticity and sphincter disturbance (p=0.05). The multivariate logistic test showed that only the beginning of lower limb weakness along with tremor was associated with PVL (OR: 2.78. 95% CI (0.99-1.02) and p=0.05). Urinary incontinence was prevalent among these patients; however, no association was identified with the HTLV-1 proviral load (PVL).

CONCLUSIONS

The absolute RT-qPCR developed for measuring HTLV-1 proviral load (PVL) demonstrated reliable results. Despite a high prevalence of urinary incontinence in these patients, no association was observed with the PVL. Consequently, it appears that HTLV-1 proviral load is specifically associated with developing spasticity in HAM/TSP.

摘要

背景

人类嗜T淋巴细胞病毒1型（HTLV-1）前病毒载量作为HTLV-1相关脊髓病/热带痉挛性截瘫（HAM/TSP）预后生物标志物的意义一直存在争议。本研究旨在评估HTLV-1前病毒载量（PVL）对HAM/TSP患者临床结局的影响。

方法

采用TaqMan方法开发了一种绝对定量HTLV-1 PVL RT-qPCR，其灵敏度和特异性均为100%。然后，从2005年至2018年，对90例符合条件的新诊断HAM/TSP患者的HTLV-1 PVL进行评估，分析其人口统计学特征、临床症状及其与HTLV-1-PVL的关联。

结果

所设计的RT-qPCR质量控制显示灵敏度和特异性均为100%。观察到58.9%的HAM/TSP患者有下肢痉挛，17.8%有泌尿系统症状。使用该设计的RT-qPCR，HTLV-1-PVL对痉挛和括约肌功能障碍有强烈影响（p=0.05）。多因素逻辑检验显示，只有下肢无力伴震颤的起病与PVL相关（比值比：2.78，95%置信区间（0.99-1.0），p=0.05）。这些患者中尿失禁很常见；然而，未发现与HTLV-1前病毒载量（PVL）有关联。

结论

为测量HTLV-1前病毒载量（PVL）而开发的绝对RT-qPCR结果可靠。尽管这些患者中尿失禁患病率很高，但未观察到与PVL有关联。因此，HTLV-1前病毒载量似乎与HAM/TSP中痉挛的发生有特异性关联。