HIV Neurobehavioral Research Center (HNRC), University of California San Diego, San Diego, CA 92093, USA.
Int J Mol Sci. 2023 Feb 1;24(3):2832. doi: 10.3390/ijms24032832.
The accumulation of soluble proteins and metabolites during wakefulness and their clearance during sleep via the glymphatic system occurs in healthy adults and is disturbed in some neurological conditions. Such diurnal variations in the cerebrospinal fluid (CSF) proteins produced outside the central nervous system and entering via the blood-brain barrier (BBB) have not been evaluated in people with HIV (PWH). CSF and blood were collected in 165 PWH at six US centers between 2003 and 2007. The time of collection was compared to CSF albumin, globulin, and total protein concentrations using bivariate and multivariate regression. Participants all took antiretroviral therapy (ART) and were mostly middle-aged (median age 44.0 years) men (78.8%), with AIDS (77.0%), plasma HIV RNA ≤ 200 copies/mL (75.8%), and immune recovery (median CD4+ T-cell count 414/µL). CSF was collected at median 1:10 p.m. (range 9:00 a.m. to 5:20 p.m.) and within a median of 15 min of blood collection. A later time of CSF collection was associated with higher total protein ( = 0.0077) and albumin ( = 0.057) in CSF but not in serum, and was additionally associated with higher CSF globulin ( = 0.013). The glymphatic clearance of albumin, globulin, and total protein is preserved in PWH. The analyses of soluble biomarkers in CSF should account for the time of collection.
在健康成年人中，清醒时可溶性蛋白和代谢物的积累以及通过神经胶质淋巴系统在睡眠时的清除作用是存在的，而在一些神经疾病中则会受到干扰。在 HIV 感染者（PWH）中，尚未评估通过血脑屏障（BBB）进入中枢神经系统的脑脊液（CSF）中由中枢神经系统以外产生的蛋白质在白天的变化。在 2003 年至 2007 年间，在美国 6 个中心收集了 165 名 PWH 的 CSF 和血液。使用双变量和多变量回归比较了收集时间与 CSF 白蛋白、球蛋白和总蛋白浓度的关系。所有参与者均接受了抗逆转录病毒治疗（ART），且大多数为中年（中位年龄 44.0 岁）男性（78.8%），患有艾滋病（77.0%），血浆 HIV RNA ≤ 200 拷贝/mL（75.8%），且免疫恢复（中位 CD4+T 细胞计数 414/µL）。CSF 采集时间中位数为下午 1:10（范围上午 9:00 至下午 5:20），距离血液采集的中位时间为 15 分钟。CSF 采集时间较晚与 CSF 中总蛋白（ = 0.0077）和白蛋白（ = 0.057）升高相关，但与血清中蛋白无关联，且与 CSF 球蛋白升高相关（ = 0.013）。PWH 的白蛋白、球蛋白和总蛋白的神经胶质淋巴清除作用是保留的。在 CSF 中分析可溶性生物标志物时，应考虑采集时间。
