Plasma Concentration of the Neurofilament Light Protein (NFL) is a Biomarker of CNS Injury in HIV Infection: A Cross-Sectional Study.
Plasma Concentration of the Neurofilament Light Protein (NFL) is a Biomarker of CNS Injury in HIV Infection: A Cross-Sectional Study.
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DOI：
10.1016/j.ebiom.2015.11.036
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发表时间：
2016-01
期刊：
影响因子：
11.1
通讯作者：
Zetterberg H
中科院分区：
文献类型：
--
作者：
Gisslén M;Price RW;Andreasson U;Norgren N;Nilsson S;Hagberg L;Fuchs D;Spudich S;Blennow K;Zetterberg H
脑脊液（CSF）神经丝轻链蛋白（NFL）是多种神经退行性疾病中神经元损伤的敏感标志物，包括在未经治疗的HIV感染中常见的CNS功能障碍损伤。然而，一个重要的限制是需要腰椎穿刺。因此，一种灵敏可靠的中枢神经系统损伤血液生物标志物将代表临床和研究环境中的一个受欢迎的进展。为了探索NFL的血浆浓度是否可用于检测HIV感染中的CNS损伤，开发了超灵敏的单分子阵列（Simoa）免疫测定法。采用横断面设计，我们测量了121例HIV感染受试者的配对CSF和血浆样本中的NFL，这些受试者根据其全身疾病的阶段、是否存在明显的HIV相关性痴呆（HAD）以及抗逆转录病毒治疗（ART）诱导的病毒抑制而分组。还检查了HIV阴性对照。血浆和脑脊液NFL浓度呈高度相关（r = 0.89，P < 0.0001）。虽然血浆NFL比CSF低50倍以上，但在所有受试者中均在新血浆测定的可定量范围内，包括HIV阴性和CSF NFL浓度正常的HIV阳性受试者。血浆和CSF中的NFL变化模式几乎相同，两者均表现出相似的年龄相关浓度增加沿着HAD中的最高值和低血CD 4 + T细胞的ART初治神经无症状受试者中的显著升高。这些结果表明，血浆NFL可能被证明是一个有价值的工具，以评估正在进行的CNS损伤的HIV感染，可应用于临床和研究设置，以评估是否存在活动性CNS损伤。由于CSF NFL在各种其他CNS疾病中也升高，因此血浆NFL的敏感措施在其他情况下也可能同样有用。血浆NFL是神经元损伤的敏感标志物血浆和CSF NFL浓度高度相关血浆NFL可用于检测治疗和未治疗的HIV中的活动性轴突损伤长期以来一直在寻找神经元损伤的敏感血液生物标志物。在这里，我们描述了一个超灵敏的定量测量的轴突神经丝轻链蛋白（NFL）在血液中。我们在HIV脑损伤的背景下测试这一点，其中脑脊液（CSF）NFL已被很好地表征，并指出是神经元损伤的可靠生物标志物。血液和CSF NFL高度相关，血浆NFL的测量能够检测HIV中严重和亚临床神经元损伤。CSF NFL在广泛的其他神经退行性疾病中升高，因此报告的发现可能具有更广泛的意义，尽管这需要额外的直接研究。
Cerebrospinal fluid (CSF) neurofilament light chain protein (NFL) is a sensitive marker of neuronal injury in a variety of neurodegenerative conditions, including the CNS dysfunction injury that is common in untreated HIV infection. However, an important limitation is the requirement for lumbar puncture. For this reason, a sensitive and reliable blood biomarker of CNS injury would represent a welcome advance in both clinical and research settings. To explore whether plasma concentrations of NFL might be used to detect CNS injury in HIV infection, an ultrasensitive Single molecule array (Simoa) immunoassay was developed. Using a cross-sectional design, we measured NFL in paired CSF and plasma samples from 121 HIV-infected subjects divided into groups according to stage of their systemic disease, presence of overt HIV-associated dementia (HAD), and after antiretroviral treatment (ART)-induced viral suppression. HIV-negative controls were also examined. Plasma and CSF NFL concentrations were very highly correlated (r = 0.89, P < 0.0001). While NFL was more than 50-fold lower plasma than CSF it was within the quantifiable range of the new plasma assay in all subjects, including the HIV negatives and the HIV positives with normal CSF NFL concentrations. The pattern of NFL changes were almost identical in plasma and CSF, both exhibiting similar age-related increases in concentrations along with highest values in HAD and substantial elevations in ART-naïve neuroasymptomatic subjects with low blood CD4+ T cells. These results show that plasma NFL may prove a valuable tool to evaluate ongoing CNS injury in HIV infection that may be applied in the clinic and in research settings to assess the presence if active CNS injury. Because CSF NFL is also elevated in a variety of other CNS disorders, sensitive measures of plasma NFL may similarly prove useful in other settings. Plasma NFL is a sensitive marker of neuronal injury Plasma and CSF NFL concentrations were highly correlated Plasma NFL is useful to detect active axonal injury in treated and untreated HIV A sensitive blood biomarker of neuronal injury has long been sought for. Here we describe an ultrasensitive quantification measurement of the axonal neurofilament light chain protein (NFL) in blood. We test this in the setting of HIV brain injury in which cerebrospinal fluid (CSF) NFL has been well characterized and noted to be a reliable biomarker of neuronal injury. Blood and CSF NFL were highly correlated and measurement of plasma NFL was able to detect both severe and subclinical neuronal injury in HIV. CSF NFL is elevated in a wide range of additional neurodegenerative settings, so the reported findings likely have broader implications, though this requires additional direct study.