Central and peripheral markers of neurodegeneration and monocyte activation in HIV-associated neurocognitive disorders.
Central and peripheral markers of neurodegeneration and monocyte activation in HIV-associated neurocognitive disorders.
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DOI：
10.1007/s13365-015-0333-3
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发表时间：
2015-08
影响因子：
3.2
通讯作者：
CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) group
中科院分区：
文献类型：
--
作者：
McGuire JL;Gill AJ;Douglas SD;Kolson DL;CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) group
HIV相关的神经认知障碍（HAND）影响高达50%的HIV感染的成人，独立地预测HIV发病率/死亡率，并且与神经元损伤和单核细胞活化相关。脑脊液神经丝亚单位（NFL，pNFH）是神经退行性疾病中神经元损伤的敏感替代标志物。在HIV中，CSF NFL在有和没有认知障碍的个体中升高，表明HIV感染期间的早期/持续性神经元损伤。尽管严重认知障碍（HIV相关痴呆（HAD））患者的CSF NFL水平高于认知正常的HIV感染者，但认知障碍严重程度、单核细胞活化、神经丝表达和全身感染之间的关系尚不清楚。我们对48名患有不同程度认知障碍、未接受抗逆转录病毒治疗（ART）的HIV感染成人进行了一项回顾性横断面研究，这些患者参加了CNS抗逆转录病毒治疗效果研究（CHARTER）。我们定量了配对CSF/血浆样本中的NFL、pNFH和单核细胞活化标志物（sCD 14/sCD 163）。通过检查ART的受试者，这些相关性不会被ART对炎症和神经变性的可能影响所混淆。我们发现HAD患者的CSF NFL水平高于CD 4 + T淋巴细胞最低值≤200的认知正常或轻度受损患者。此外，CSF NFL水平与血浆HIV-1 RNA病毒载量显著正相关，与血浆CD 4 + T淋巴细胞计数呈负相关，表明神经元损伤与系统性HIV感染之间存在联系。最后，CSF NFL与CSF pNFH、sCD 163和sCD 14显著正相关，表明CNS隔室内的单核细胞活化与HAND所有阶段的神经元损伤直接相关。
HIV-associated neurocognitive disorders (HAND) affect up to 50 % of HIV-infected adults, independently predict HIV morbidity/mortality, and are associated with neuronal damage and monocyte activation. Cerebrospinal fluid (CSF) neurofilament subunits (NFL, pNFH) are sensitive surrogate markers of neuronal damage in several neurodegenerative diseases. In HIV, CSF NFL is elevated in individuals with and without cognitive impairment, suggesting early/persistent neuronal injury during HIV infection. Although individuals with severe cognitive impairment (HIV-associated dementia (HAD)) express higher CSF NFL levels than cognitively normal HIV-infected individuals, the relationships between severity of cognitive impairment, monocyte activation, neurofilament expression, and systemic infection are unclear. We performed a retrospective cross-sectional study of 48 HIV-infected adults with varying levels of cognitive impairment, not receiving antiretroviral therapy (ART), enrolled in the CNS Anti-Retroviral Therapy Effects Research (CHARTER) study. We quantified NFL, pNFH, and monocyte activation markers (sCD14/sCD163) in paired CSF/plasma samples. By examining subjects off ART, these correlations are not confounded by possible effects of ART on inflammation and neurodegeneration. We found that CSF NFL levels were elevated in individuals with HAD compared to cognitively normal or mildly impaired individuals with CD4+ T-lymphocyte nadirs ≤200. In addition, CSF NFL levels were significantly positively correlated to plasma HIV-1 RNA viral load and negatively correlated to plasma CD4+ T-lymphocyte count, suggesting a link between neuronal injury and systemic HIV infection. Finally, CSF NFL was significantly positively correlated with CSF pNFH, sCD163, and sCD14, demonstrating that monocyte activation within the CNS compartment is directly associated with neuronal injury at all stages of HAND.