Plasma and Cerebrospinal Fluid Biomarkers Predict Cerebral Injury in HIV-Infected Individuals on Stable Combination Antiretroviral Therapy.
Plasma and Cerebrospinal Fluid Biomarkers Predict Cerebral Injury in HIV-Infected Individuals on Stable Combination Antiretroviral Therapy.
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DOI：
10.1097/qai.0000000000000532
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发表时间：
2015-05-01
期刊：
影响因子：
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通讯作者：
HIV Neuroimaging Consortium
中科院分区：
文献类型：
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作者：
Anderson AM;Harezlak J;Bharti A;Mi D;Taylor MJ;Daar ES;Schifitto G;Zhong J;Alger JR;Brown MS;Singer EJ;Campbell TB;McMahon DD;Buchthal S;Cohen R;Yiannoutsos C;Letendre SL;Navia BA;HIV Neuroimaging Consortium
尽管进行了抗逆转录病毒治疗（cART），但HIV相关的脑损伤仍然存在，但对其影响因素仍知之甚少。我们假设炎症相关的生物标志物与慢性HIV感染者的质子磁共振波谱（MRS）脑损伤相关。在197名HIV感染者中测量了5种生物标志物：可溶性CD 14、MCP-1、IP-10、MIP-1β和fractalkine。在中额皮质（MFC）、额叶白色物质（FWM）和基底神经节（BG）中获得N-乙酰天冬氨酸（NAA）、胆碱（Cho）、肌醇（MI）、谷氨酸+谷氨酰胺（Glx）和肌酸（Cr）的水平。通过线性回归建立预测模型，并使用Akaike信息标准选择最佳模型。血浆或CSF MCP-1的增加与MFC和BG中较低的NAA/Cr相关，而FWM中NAA/Cr、GlxCr和Cho/Cr的代谢物变化几乎完全由单一因素sCD 14解释。在MFC和BG中，该因子的血浆和CSF水平也与Glx/Cr显著相关。BG中较高的CSF FKN与较高的NAA/Cr相关。BG和MFC中较高Cho/Cr的最佳预测因子是CSF sCD 14和CSF MIP-1β。血浆和CSF IP-10仅与MFC中的Cho/Cr相关。在同时考虑血浆和CSF的三种模型中，CSF生物标志物与MRS代谢物之间存在更多关联。炎症和免疫激活标志物，特别是MCP-1和sCD 14，主要反映CNS来源，在接受稳定cART的慢性HIV感染患者中以代谢物和区域依赖性方式导致脑损伤持续存在。
HIV-associated brain injury persists despite antiretroviral therapy (cART), but contributing factors remain poorly understood. We postulated that inflammation-associated biomarkers will be associated with cerebral injury on proton magnetic resonance spectroscopy (MRS) in chronically HIV-infected subjects. Five biomarkers were measured in 197 HIV-infected subjects: soluble CD14, MCP-1, IP-10, MIP-1β, and fractalkine. Levels of N-acetyl aspartate (NAA), Choline (Cho), Myoinositol (MI), Glutamate+Glutamine (Glx), and Creatine (Cr) were acquired in the midfrontal cortex (MFC), frontal white matter (FWM), and basal ganglia (BG). Predictive models were built via linear regression and the best models were chosen using the Akaike Information Criterion. Increases in plasma or CSF MCP-1 were associated with lower NAA/Cr in the MFC and BG while metabolite changes in the FWM for NAA/Cr, GlxCr and Cho/Cr were explained almost exclusively by a single factor, sCD14. Plasma and CSF levels of this factor were also significantly associated with Glx/Cr in MFC and BG. Higher CSF FKN was associated with higher NAA/Cr in BG. Best predictors for higher Cho/Cr in BG and MFC were CSF sCD14 and CSF MIP-1β. Plasma and CSF IP-10 were only associated with Cho/Cr in MFC. Of the three models that simultaneously accounted for both plasma and CSF, there were more associations between CSF biomarkers and MRS metabolites. Markers of inflammation and immune activation, in particular MCP-1 and sCD14, predominantly reflecting CNS sources, contribute to the persistence of brain injury in a metabolite and region dependent manner in chronically HIV-infected patients on stable cART.