A peripheral monocyte interferon phenotype in HIV infection correlates with a decrease in magnetic resonance spectroscopy metabolite concentrations.
A peripheral monocyte interferon phenotype in HIV infection correlates with a decrease in magnetic resonance spectroscopy metabolite concentrations.
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HIV感染中的外周单核细胞干扰素表型与磁共振波谱代谢物浓度的降低相关。
DOI：
10.1097/qad.0b013e328349f022
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发表时间：
2011
期刊：
影响因子：
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通讯作者：
Meyerhoff,DieterJ
中科院分区：
文献类型：
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作者：
Pulliam,Lynn;Rempel,Hans;Sun,Bing;Abadjian,Linda;Calosing,Cyrus;Meyerhoff,DieterJ
目的：尽管有有效的抗逆转录病毒治疗(ART)，但仍有35%以上的HIV感染者认知功能受损。我们调查了外周免疫激活和大脑代谢物浓度之间的可能联系。设计和方法：35名HIV血清阳性(HIV+)和8名HIV血清阴性的成年人参加了这项横断面研究。所有HIV阳性患者都在接受抗逆转录病毒治疗或中断治疗。参与者使用4特斯拉短回声时间质子磁共振波谱对单核细胞基因表达、认知状态和大脑代谢物浓度进行了评估。结果：单核细胞基因芯片分析显示，单核细胞基因芯片显示干扰素-α诱导的激活表型。对HIV反应增加最多的14个基因是干扰素基因。通过基因表达谱测量的单核细胞激活与FWM中较低的N-乙酰天冬氨酸(NAA)密切相关。干扰素应答基因干扰素-γ诱导蛋白-10(IP-10)在HIV患者的单核细胞中被激活，并与血浆蛋白水平密切相关。血浆IP-10与ACC NAA呈显著负相关，轻度HIV阳性患者血浆IP-10水平低于无认知损害患者。结论：I型干扰素诱导的慢性外周免疫激活与FWM和ACC神经元损伤及认知功能障碍有关。易于检测的干扰素诱导的血液标志物在早期神经细胞损伤中可能具有临床意义。
Objective:In spite of effective antiretroviral therapy (ART), cognition is impaired in upwards of 35% of the HIV-infected population. We investigated a possible link between peripheral immune activation and brain metabolite concentrations.Design and methods:Thirty-five HIV-seropositive (HIV+) and eight HIV-seronegative adults were recruited to this cross-sectional study. All HIV-positive patients were on ART or a treatment interruption. Participants were evaluated for monocyte gene expression, cognitive status, and brain metabolite concentrations using 4-Tesla short echo-time proton magnetic resonance spectroscopy. Absolute concentrations of brain metabolites in the frontal white matter (FWM), anterior cingulate cortex (ACC), and basal ganglia were derived and related to monocyte gene expression and global deficit scores.Results:Analysis of monocyte gene arrays revealed an interferon (IFN)-α-induced activation phenotype. Fourteen genes having the greatest fold increase in response to HIV were IFN genes. Monocyte activation as measured by gene expression profiles strongly correlated with lower N-acetylaspartate (NAA) in FWM. The IFN response gene Interferon-gamma inducible protein-10 (IP-10) was activated in monocytes from HIV individuals and strongly correlated with plasma protein levels. Plasma IP-10 correlated significantly and inversely with ACC NAA, which was lower in HIV-positive patients with mild compared to no cognitive impairment.Conclusion:Chronic peripheral immune activation driven by a type 1 IFN correlates with neuronal injury in FWM and ACC and cognitive dysfunction. Easily measured IFN-induced blood markers may be clinically significant in following early neural cell damage.