Cerebrospinal Fluid and Neuroimaging Biomarker Abnormalities Suggest Early Neurological Injury in a Subset of Individuals During Primary HIV Infection
Cerebrospinal Fluid and Neuroimaging Biomarker Abnormalities Suggest Early Neurological Injury in a Subset of Individuals During Primary HIV Infection
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DOI：
10.1093/infdis/jit088
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发表时间：
2013-06-01
影响因子：
6.4
通讯作者：
Spudich, Serena
中科院分区：
文献类型：
--
作者：
Peluso, Michael J.;Meyerhoff, Dieter J.;Spudich, Serena
背景。脑脊液 (CSF) 和神经影像学异常表明慢性 AIDS 期间的神经元损伤，但原发性人类免疫缺陷病毒 (HIV) 感染期间这些生物标志物的数据有限。 方法。我们比较了 92 名原发性 HIV 感染者和 25 名对照者的脑脊液中神经丝轻链、t-tau、p-tau、淀粉样前体蛋白和淀粉样蛋白-β 42 的浓度。我们检查了疾病进展和神经炎症、神经心理学测试和基于质子磁共振波谱 (MRS) 的代谢物之间的关系。结果。与对照组相比，原发性 HIV 感染者的神经丝轻链升高 (P = .0004)，并与脑脊液新蝶呤 (r = 0.38；P = .0005)、干扰素 γ 诱导蛋白 10 (r = 0.39；P = .002)、白细胞 (r = 0.32；P = .004)、蛋白质 (r = 0.59；P < .0001) 和脑脊液/血浆白蛋白比率 (r = 0.60; P < .0001)。神经丝轻链与前扣带回 N-乙酰天门冬氨酸/肌酸和谷氨酸/肌酸减少相关（分别为 r = -0.35，P = .02；r = -0.40，P = .009）、额叶白质（分别为 r = -0.43，P = .003；r = -0.30，P = .048）和顶叶灰质（r = -0.43，P = .003；r = -0.47，P = .001）。 β-淀粉样蛋白在原发感染组中升高 (P = .0005)，并与感染时间相关 (r = 0.34；P = .003)。这两种标志物均与神经心理学异常相关。 T-tau 和可溶性淀粉样前体蛋白在各组之间没有差异。结论。神经丝轻链升高及其与基于 MRS 的代谢物的相关性表明，原发性 HIV 感染的一部分参与者通过涉及中枢神经系统炎症的机制发生早期神经元损伤。
Background. Cerebrospinal fluid (CSF) and neuroimaging abnormalities demonstrate neuronal injury during chronic AIDS, but data on these biomarkers during primary human immunodeficiency virus (HIV) infection is limited.Methods. We compared CSF concentrations of neurofilament light chain, t-tau, p-tau, amyloid precursor proteins, and amyloid-beta 42 in 92 subjects with primary HIV infection and 25 controls. We examined relationships with disease progression and neuroinflammation, neuropsychological testing, and proton-magnetic resonance spectroscopy (MRS)-based metabolites.Results. Neurofilament light chain was elevated in primary HIV infection compared with controls (P = .0004) and correlated with CSF neopterin (r = 0.38; P = .0005), interferon gamma-induced protein 10 (r = 0.39; P = .002), white blood cells (r = 0.32; P = .004), protein (r = 0.59; P < .0001), and CSF/plasma albumin ratio (r = 0.60; P < .0001). Neurofilament light chain correlated with decreased N-acteylaspartate/creatine and glutamate/creatine in the anterior cingulate (r = -0.35, P = .02; r = -0.40, P = .009, respectively), frontal white matter (r = -0.43, P = .003; r = -0.30, P = .048, respectively), and parietal gray matter (r = -0.43, P = .003; r = -0.47, P = .001, respectively). Beta-amyloid was elevated in the primary infection group (P = .0005) and correlated with time infected (r = 0.34; P = .003). Neither marker correlated with neuropsychological abnormalities. T-tau and soluble amyloid precursor proteins did not differ between groups.Conclusions. Elevated neurofilament light chain and its correlation with MRS-based metabolites suggest early neuronal injury in a subset of participants with primary HIV infection through mechanisms involving central nervous system inflammation.