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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?

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?

作者信息

Martins Marina Lobato, Guimarães Jacqueline Cronemberger, Ribas João Gabriel, Romanelli Luiz Cláudio Ferreira, de Freitas Carneiro-Proietti Anna Bárbara

机构信息

Research Department, Minas Gerais State Blood Center (Fundação Hemominas), Belo Horizonte, Brazil.

Interdisciplinary HTLV Research Group (GIPH), Belo Horizonte, Brazil.

出版信息

J Neurovirol. 2017 Feb;23(1):125-133. doi: 10.1007/s13365-016-0484-x. Epub 2016 Sep 27.

Abstract

HTLV-1 proviral load (pvl) is an important risk marker for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), but its value as prognostic marker is not well defined. Long-term prospective cohort studies are necessary to clarify this question. Here, we analyzed HTLV-1 pvl in the peripheral blood of 82 asymptomatic carriers (AC; 351 samples), 12 HAM/TSP patients (HAM; 46 samples), and six incident cases of HAM/TSP (iHAM), with serial samples collected before (n = 10) and after (n = 20) the disease onset. The mean interval of follow-up was 10 years in the AC group and 8 years in HAM and iHAM groups. pvl was not significantly different between the first and last measurements in the three groups, but there was a trend to decrease over time. Coefficient of variation of pvl was significantly lower in the AC group than in HAM (p = 0.015) and iHAM (p = 0.022) patients. AC and HAM individuals showed a significant and strong positive correlation between the first and last measurements of pvl, but not iHAM subjects. All individuals who developed HAM/TSP during the follow-up had high pvl level (>1 %) before the onset of disease, but a typical increase in pvl was not observed in that period. The data suggest that there is a trend to reach an equilibrium plateau of pvl over time, characteristic of each individual. A significant rate of AC keeps high pvl levels for a long time without developing clinical symptoms associated to HTLV-1 infection. Thus, serial quantification of pvl in the peripheral blood does not seem to be a good prognostic marker for HAM/TSP.

摘要

人嗜T淋巴细胞病毒1型(HTLV-1)前病毒载量(pvl)是HTLV-1相关脊髓病/热带痉挛性截瘫(HAM/TSP)的一个重要风险标志物,但其作为预后标志物的价值尚未明确界定。需要长期前瞻性队列研究来阐明这个问题。在此,我们分析了82名无症状携带者(AC;351份样本)、12名HAM/TSP患者(HAM;46份样本)和6例HAM/TSP新发病例(iHAM)外周血中的HTLV-1 pvl,在疾病发作前(n = 10)和发作后(n = 20)采集了系列样本。AC组的平均随访间隔为10年,HAM组和iHAM组为8年。三组首次和末次测量的pvl无显著差异,但有随时间下降的趋势。AC组pvl的变异系数显著低于HAM组(p = 0.015)和iHAM组(p = 0.022)患者。AC组和HAM组个体pvl的首次和末次测量之间存在显著且强烈的正相关,但iHAM组个体不存在。所有在随访期间发生HAM/TSP的个体在疾病发作前pvl水平都很高(>1%),但在此期间未观察到pvl的典型升高。数据表明,随着时间推移,pvl有达到平衡平台期的趋势,这是每个个体的特征。相当比例的AC长期保持高pvl水平,而未出现与HTLV-1感染相关的临床症状。因此,外周血中pvl的系列定量似乎不是HAM/TSP的良好预后标志物。

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