Biomarker evidence of axonal injury in neuroasymptomatic HIV-1 patients.
Biomarker evidence of axonal injury in neuroasymptomatic HIV-1 patients.
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DOI：
10.1371/journal.pone.0088591
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Gisslén M
中科院分区：
文献类型：
--
作者：
Jessen Krut J;Mellberg T;Price RW;Hagberg L;Fuchs D;Rosengren L;Nilsson S;Zetterberg H;Gisslén M
据报道，HIV-1感染患者中神经认知障碍的患病率很高。目前尚不清楚这是否是艾滋病毒相关的活跃神经变性所致。我们用一种新的、灵敏的方法检测了HIV-1患者的轴突损伤，方法是测量脑脊液中神经丝蛋白的轻亚单位(NFL)。采用横断面设计，分析了252例HIV感染者脑脊液中神经丝蛋白光(NFL)、新喋呤(鞘内免疫激活)和脑脊液/血浆白蛋白比值(血脑屏障完整性)的浓度，并将其细分为未经治疗的神经症状组(n = 200例)、HIV相关性痴呆(HAD组)(n = 14例)和联合抗逆转录病毒治疗(CART)组(n = 85例)，以及健康对照组(n = 204例)。46名HIV感染患者同时被纳入治疗组和未治疗组，但在不同的时间点进行了抽样。此外，对78例无神经症状的患者在开始治疗前后进行了分析。虽然HAD患者的NFL浓度最高，但33%的未经治疗的神经无症状患者的脑脊液NFL水平也升高，主要发生在外周血中CD_4+细胞数低于250cell/μL的患者。在未治疗组中，新喋呤与NFL水平相关，而在未治疗组和治疗组中，白蛋白比率与NFL相关。在许多无神经症状的患者中，脑脊液NFL升高提示持续的轴突损伤。治疗降低了NFL，但接受治疗的患者保持了比对照组更高的水平，这表明要么是持续的病毒相关损伤，要么是艾滋病毒感染的衰老效应。NFL与新喋呤和白蛋白比率相关，提示轴突损伤、神经炎症和血脑屏障通透性之间存在关联。NFL似乎是HIV亚临床和临床脑损伤的敏感生物标志物，值得进一步评估以用于更广泛的临床应用。
Prevalence of neurocognitive impairment in HIV-1 infected patients is reported to be high. Whether this is a result of active HIV-related neurodegeneration is unclear. We examined axonal injury in HIV-1 patients by measuring the light subunit of neurofilament protein (NFL) in CSF with a novel, sensitive method. With a cross-sectional design, CSF concentrations of neurofilament protein light (NFL) (marker of neuronal injury), neopterin (intrathecal immunoactivation) and CSF/Plasma albumin ratio (blood-brain barrier integrity) were analyzed on CSF from 252 HIV-infected patients, subdivided into untreated neuroasymptomatics (n = 200), HIV-associated dementia (HAD) (n = 14) and on combinations antiretroviral treatment (cART) (n = 85), and healthy controls (n = 204). 46 HIV-infected patients were included in both treated and untreated groups, but sampled at different timepoints. Furthermore, 78 neuroasymptomatic patients were analyzed before and after treatment initiation. While HAD patients had the highest NFL concentrations, elevated CSF NFL was also found in 33% of untreated neuroasymptomatic patients, mainly in those with blood CD4+ cell counts below 250 cells/μL. CSF NFL concentrations in the untreated neuroasymptomatics and treated groups were equivalent to controls 18.5 and 3.9 years older, respectively. Neopterin correlated with NFL levels in untreated groups while the albumin ratio correlated with NFL in both untreated and treated groups. Increased CSF NFL indicates ongoing axonal injury in many neuroasymptomatic patients. Treatment decreases NFL, but treated patients retain higher levels than controls, indicating either continued virus-related injury or an aging-like effect of HIV infection. NFL correlates with neopterin and albumin ratio, suggesting an association between axonal injury, neuroinflammation and blood-brain barrier permeability. NFL appears to be a sensitive biomarker of subclinical and clinical brain injury in HIV and warrants further assessment for broader clinical use.
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影响因子：
3.2
作者：
Heaton, Robert K.;Franklin, Donald R.;Ellis, Ronald J.;McCutchan, J. Allen;Letendre, Scott L.;LeBlanc, Shannon;Corkran, Stephanie H.;Duarte, Nichole A.;Clifford, David B.;Woods, Steven P.;Collier, Ann C.;Marra, Christina M.;Morgello, Susan;Mindt, Monica Rivera;Taylor, Michael J.;Marcotte, Thomas D.;Atkinson, J. Hampton;Wolfson, Tanya;Gelman, Benjamin B.;McArthur, Justin C.;Simpson, David M.;Abramson, Ian;Gamst, Anthony;Fennema-Notestine, Christine;Jernigan, Terry L.;Wong, Joseph;Grant, Igor
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Grant, Igor
影响因子：
11.2
作者：
POWER, C;KONG, PA;TRAPP, BD
通讯作者：
TRAPP, BD
影响因子：
105.7
作者：
PORTEGIES, P;DEGANS, J;GOUDSMIT, J
通讯作者：
GOUDSMIT, J
影响因子：
9.9
作者：
MCARTHUR, JC;NANCESPROSON, TE;SAAH, A
通讯作者：
SAAH, A
影响因子：
9.9
作者：
Cysique, L. A.;Vaida, F.;Ellis, R. J.
通讯作者：
Ellis, R. J.