Department of Radiology, Northwestern University, 737 North Michigan Avenue, Suite 1600, Chicago, IL, 60611, USA.
J Neurovirol. 2013 Oct;19(5):452-60. doi: 10.1007/s13365-013-0197-3. Epub 2013 Aug 27.
Matrix metalloproteinases (MMPs) have been implicated in human immunodeficiency virus (HIV)-associated neurological injury; however, this relationship has not been studied early in infection. Plasma levels of MMP-1, MMP-2, MMP-7, MMP-9, and MMP-10 measured using Luminex technology (Austin, TX, USA) were compared in 52 HIV and 21 seronegative participants of the Chicago Early HIV Infection study. MMP levels were also examined in HIV subgroups defined by antibody reactivity, viremia, and antiretroviral status, as well as in available cerebrospinal fluid (CSF) samples (n = 9). MMPs were evaluated for patterns of relationship to cognitive function and to quantitative magnetic resonance measurements of the brain derived in vivo. Plasma MMP-2 levels were significantly reduced in early HIV infection and correlated with altered white matter integrity and atrophic brain changes. MMP-9 levels were higher in the treated subgroup than in the naïve HIV subgroup. Only MMP-2 and MMP-9 were detected in the CSF; CSF MMP-2 correlated with white matter integrity and with volumetric changes in basal ganglia. Relationships with cognitive function were also identified. MMP-2 levels in plasma and in CSF correspond to early changes in brain structure and function. These findings establish a link between MMPs and neurological status previously unidentified in early HIV infection.
基质金属蛋白酶(MMPs)与人类免疫缺陷病毒(HIV)相关的神经损伤有关;然而,在感染早期尚未对此关系进行研究。使用 Luminex 技术(美国得克萨斯州奥斯汀)比较了 52 名 HIV 感染者和 21 名血清阴性的芝加哥早期 HIV 感染研究参与者的血浆 MMP-1、MMP-2、MMP-7、MMP-9 和 MMP-10 水平。还检查了根据抗体反应性、病毒血症和抗逆转录病毒状态以及可用的脑脊液(CSF)样本(n=9)定义的 HIV 亚组中的 MMP 水平。评估了 MMP 与认知功能以及体内定量磁共振测量的大脑之间关系的模式。在 HIV 感染早期,血浆 MMP-2 水平显著降低,与白质完整性改变和萎缩性脑改变相关。治疗亚组的 MMP-9 水平高于未治疗 HIV 亚组。仅在 CSF 中检测到 MMP-2 和 MMP-9;CSF MMP-2 与白质完整性和基底神经节体积变化相关。还确定了与认知功能的关系。血浆和 CSF 中的 MMP-2 水平与脑结构和功能的早期变化相对应。这些发现确立了 MMPs 与以前在 HIV 感染早期未被识别的神经状态之间的联系。