Molecular Medicine Postgraduate Program, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil.
HTLV-1 Research Interdisciplinary Group (GIPH), Hemominas Foundation, Belo Horizonte, Minas Gerais, Brazil.
PLoS Negl Trop Dis. 2018 Aug 27;12(8):e0006720. doi: 10.1371/journal.pntd.0006720. eCollection 2018 Aug.
HTLV-1 infection is endemic in Brazil. About 1 to 2% of the Brazilian population is estimated to be infected, but most infected HTLV-1 individuals do not know about their own infection, which favors the continuity of sexual and vertical virus transmission. In addition, HTLV-1 associated central nervous system diseases and their pathophysiologic mechanisms are not fully understood. This study aimed to evaluate the correlation of spinal cord metabolism, viral and inflammatory profiles with features of neurological presentation in HTLV-1 infected individuals.
This is a cross-sectional study of a cohort including 48 HTLV-1 infected individuals clinically classified as asymptomatic-AG (N = 21), symptomatic-SG (N = 11) and HAM/TSP-HG (N = 16) and a nested case-control study with HTLV-1 infected individuals-HIG (N = 48) and HTLV-1 non infected controls-CG (N = 30) that had their spinal cord analysed by Positron Emission Tomography with 18F-Fluordeoxyglucose (18F-FDG PET/CT). HTLV-1 infected individuals had 18F-FDG PET/CT results analyzed with clinical and demographic data, proviral load, cytokines and chemokines in the blood and cerebrospinal fluid (CSF).
18F-FDG PET/CT showed hypometabolism in the thoracic spinal cord in HTLV-1 infected individuals. The method had an accuracy of 94.4% to identify HAM/TSP. A greater involvement of the thoracic spinal cord was observed, although hypometabolism was also observed in the cervical spinal cord segment in HTLV-1 infected individuals. Individuals with HAM/TSP showed a pro-inflammatory profile in comparison to asymptomatic and symptomatic groups, with a higher level of Interferon-inducible T-cell alpha chemoattractant (ITAC/CXCL11), IL-6, IL-12p70 in the plasma; and ITAC, IL-4, IL-5, IL-8 (CXCL8) and TNF-alpha in the CSF. Using regression, thoracic spinal cord SUV (standardized uptake value) and CSF ITAC level were identified as the HAM/TSP predictors in the multivariate model.
18F-FDG PET/CT imaging showed spinal cord hypometabolism in most HTLV-1 infected individuals, even in the asymptomatic HTLV-1 group. Thoracic spinal cord hypometabolism and CSF-ITAC levels were identified predictors of HAM/TSP.
Our findings suggested that in most HTLV-1 infected individuals there was compromise of central nervous system (CNS) structures despite of the lack of clinical symptoms. To explain the found hypometabolism, the role of microcirculatory and metabolic factors in the pathogenesis of neurological diseases associated with HTLV-1 infection must be further investigated. It is paramount to evaluate the central nervous function and to compare the performance among HTLV-1 infected individuals considered asymptomatic to the uninfected controls.
HTLV-1 感染在巴西流行。据估计，约有 1%至 2%的巴西人口受到感染，但大多数感染 HTLV-1 的个体并不知道自己的感染情况，这有利于病毒的性传播和垂直传播的持续。此外，HTLV-1 相关的中枢神经系统疾病及其病理生理机制尚未完全阐明。本研究旨在评估 HTLV-1 感染个体脊髓代谢、病毒和炎症特征与神经表现特征之间的相关性。
这是一项队列的横断面研究，包括 48 名临床分类为无症状-AG（N=21）、有症状-SG（N=11）和 HAM/TSP-HG（N=16）的 HTLV-1 感染个体，以及嵌套病例对照研究包括 HTLV-1 感染个体-HIG（N=48）和 HTLV-1 未感染对照-CG（N=30），对他们的脊髓进行正电子发射断层扫描 18F-氟脱氧葡萄糖（18F-FDG PET/CT）分析。对 HTLV-1 感染个体的 18F-FDG PET/CT 结果进行分析，同时分析临床和人口统计学数据、前病毒载量、血液和脑脊液中的细胞因子和趋化因子。
18F-FDG PET/CT 显示 HTLV-1 感染个体的胸段脊髓代谢低下。该方法对 HAM/TSP 的识别准确率为 94.4%。尽管在 HTLV-1 感染个体的颈段脊髓也观察到代谢低下，但观察到胸段脊髓的受累更严重。与无症状和有症状组相比，HAM/TSP 个体表现出前炎症特征，血浆中干扰素诱导的 T 细胞α趋化因子（ITAC/CXCL11）、IL-6、IL-12p70 水平更高；CSF 中 ITAC、IL-4、IL-5、IL-8（CXCL8）和 TNF-α水平更高。使用回归，胸段脊髓 SUV（标准化摄取值）和 CSF ITAC 水平被确定为多变量模型中 HAM/TSP 的预测因子。
18F-FDG PET/CT 成像显示大多数 HTLV-1 感染个体的脊髓代谢低下，即使在无症状 HTLV-1 组也是如此。胸段脊髓代谢低下和 CSF-ITAC 水平是 HAM/TSP 的预测因子。
我们的研究结果表明，尽管大多数 HTLV-1 感染个体没有临床症状，但中枢神经系统（CNS）结构仍受到损害。为了解释发现的代谢低下，必须进一步研究微循环和代谢因素在与 HTLV-1 感染相关的神经疾病发病机制中的作用。评估中枢神经系统功能并比较被认为无症状的 HTLV-1 感染个体与未感染对照之间的表现非常重要。
