HIV 感染中的血脑屏障完整性、鞘内免疫激活及神经元损伤
Blood-brain barrier integrity, intrathecal immunoactivation, and neuronal injury in HIV.
作者信息
Anesten Birgitta, Yilmaz Aylin, Hagberg Lars, Zetterberg Henrik, Nilsson Staffan, Brew Bruce J, Fuchs Dietmar, Price Richard W, Gisslén Magnus
机构信息
Department of Infectious Diseases, Institute of Biomedicine (B.A., A.Y., L.H., M.G.), and Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology (H.Z.), Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; Mathematical Sciences (S.N.), Chalmers University of Technology, Gothenburg, Sweden; Departments of Neurology and HIV Medicine (B.J.B.), St Vincent's Hospital and Peter Duncan Neurosciences Unit, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia; Division of Biological Chemistry (D.F.), Biocenter, Innsbruck Medical University, Innsbruck, Austria; and Department of Neurology (R.W.P.), University of California San Francisco.
出版信息
Neurol Neuroimmunol Neuroinflamm. 2016 Nov 9;3(6):e300. doi: 10.1212/NXI.0000000000000300. eCollection 2016 Dec.
OBJECTIVE
Although blood-brain barrier (BBB) impairment has been reported in HIV-infected individuals, characterization of this impairment has not been clearly defined.
METHODS
BBB integrity was measured by CSF/plasma albumin ratio in this cross-sectional study of 631 HIV-infected individuals and 71 controls. We also analyzed CSF and blood HIV RNA and neopterin, CSF leukocyte count, and neurofilament light chain protein (NFL) concentrations. The HIV-infected participants included untreated neuroasymptomatic patients, patients with untreated HIV-associated dementia (HAD), and participants on suppressive antiretroviral treatment (ART).
RESULTS
The albumin ratio was significantly increased in patients with HAD compared to all other groups. There were no significant differences between untreated neuroasymptomatic participants, treated participants, and controls. BBB integrity, however, correlated significantly with CSF leukocyte count, CSF HIV RNA, serum and CSF neopterin, and age in untreated neuroasymptomatic participants. In a multiple linear regression analysis, age, CSF neopterin, and CSF leukocyte count stood out as independent predictors of albumin ratio. A significant correlation was found between albumin ratio and CSF NFL in untreated neuroasymptomatic patients and in participants on ART. Albumin ratio, age, and CD4 cell count were confirmed as independent predictors of CSF NFL in multivariable analysis.
CONCLUSIONS
BBB disruption was mainly found in patients with HAD, where BBB damage correlated with CNS immunoactivation. Albumin ratios also correlated with CSF inflammatory markers and NFL in untreated neuroasymptomatic participants. These findings give support to the association among BBB deterioration, intrathecal immunoactivation, and neuronal injury in untreated neuroasymptomatic HIV-infected individuals.
目的
尽管已有报道称HIV感染者存在血脑屏障（BBB）损伤，但其损伤特征尚未明确界定。
方法
在这项横断面研究中，通过脑脊液/血浆白蛋白比值对631名HIV感染者和71名对照者的血脑屏障完整性进行了测量。我们还分析了脑脊液和血液中的HIV RNA及新蝶呤、脑脊液白细胞计数以及神经丝轻链蛋白（NFL）浓度。HIV感染参与者包括未经治疗的神经无症状患者、未经治疗的HIV相关痴呆（HAD）患者以及接受抑制性抗逆转录病毒治疗（ART）的参与者。
结果
与所有其他组相比，HAD患者的白蛋白比值显著升高。未经治疗的神经无症状参与者、接受治疗的参与者和对照者之间无显著差异。然而，在未经治疗的神经无症状参与者中，血脑屏障完整性与脑脊液白细胞计数、脑脊液HIV RNA、血清和脑脊液新蝶呤以及年龄显著相关。在多元线性回归分析中，年龄、脑脊液新蝶呤和脑脊液白细胞计数是白蛋白比值的独立预测因素。在未经治疗的神经无症状患者和接受ART治疗的参与者中，白蛋白比值与脑脊液NFL之间存在显著相关性。在多变量分析中，白蛋白比值、年龄和CD4细胞计数被确认为脑脊液NFL的独立预测因素。
结论
血脑屏障破坏主要见于HAD患者，其中血脑屏障损伤与中枢神经系统免疫激活相关。在未经治疗的神经无症状参与者中，白蛋白比值也与脑脊液炎症标志物和NFL相关。这些发现支持了未经治疗的神经无症状HIV感染者血脑屏障恶化、鞘内免疫激活和神经元损伤之间的关联。
Zotero 插件