Guha Debjani, Misra Vikas, Yin Jun, Horiguchi Miki, Uno Hajime, Gabuzda Dana
Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Department of Data Science, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
medRxiv. 2023 Jul 24:2023.07.23.23293053. doi: 10.1101/2023.07.23.23293053.
Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) remain prevalent despite viral suppression on antiretroviral therapy (ART). Vascular disease contributes to HAND, but peripheral markers that distinguish vascular cognitive impairment (VCI) from HIV-related etiologies remain unclear.
Cross-sectional study of vascular injury, inflammation, and central nervous system (CNS) injury markers in relation to HAND.
Vascular injury (VCAM-1, ICAM-1, CRP), inflammation (IFN-γ, IL-1β, IL-6, IL-8, IL-15, IP-10, MCP-1, VEGF-A), and CNS injury (NFL, total Tau, GFAP, YKL-40) markers were measured in plasma and CSF from 248 individuals (143 HIV+ on suppressive ART and 105 HIV- controls).
Median age was 53 years, median CD4 count, and duration of HIV infection were 505 cells/μl and 16 years, respectively. Vascular injury, inflammation, and CNS injury markers were increased in HIV+ compared with HIV- individuals (p<0.05). HAND was associated with increased plasma VCAM-1, ICAM-1, and YKL-40 (p<0.01) and vascular disease (p=0.004). In contrast, inflammation markers had no significant association with HAND. Vascular injury markers were associated with lower neurocognitive T scores in age-adjusted models (p<0.01). Furthermore, plasma VCAM-1 correlated with NFL (r=0.29, p=0.003). Biomarker clustering separated HAND into three clusters: two clusters with high prevalence of vascular disease, elevated VCAM-1 and NFL, and distinctive inflammation profiles (CRP/ICAM-1/YKL-40 or IL-6/IL-8/IL-15/MCP-1), and one cluster with no distinctive biomarker elevations.
Vascular injury markers are more closely related to HAND and CNS injury in PWH on suppressive ART than inflammation markers and may help to distinguish relative contributions of VCI to HAND.
尽管接受抗逆转录病毒治疗（ART）后病毒得到抑制，但人类免疫缺陷病毒（HIV）相关神经认知障碍（HAND）仍然普遍存在。血管疾病导致HAND，但区分血管性认知障碍（VCI）与HIV相关病因的外周标志物仍不明确。
关于HAND的血管损伤、炎症和中枢神经系统（CNS）损伤标志物的横断面研究。
在248名个体（143名接受抑制性ART的HIV感染者和105名HIV阴性对照者）的血浆和脑脊液中测量血管损伤（血管细胞黏附分子-1、细胞间黏附分子-1、C反应蛋白）、炎症（干扰素-γ、白细胞介素-1β、白细胞介素-6、白细胞介素-8、白细胞介素-15、干扰素诱导蛋白10、单核细胞趋化蛋白-1、血管内皮生长因子-A）和CNS损伤（神经丝轻链、总tau蛋白、胶质纤维酸性蛋白、YKL-40）标志物。
中位年龄为53岁，HIV感染的中位CD4细胞计数和持续时间分别为505个细胞/μl和16年。与HIV阴性个体相比，HIV感染者的血管损伤、炎症和CNS损伤标志物升高（p<0.05）。HAND与血浆血管细胞黏附分子-1、细胞间黏附分子-1和YKL-40升高（p<0.01）以及血管疾病（p=0.004）相关。相比之下，炎症标志物与HAND无显著关联。在年龄校正模型中，血管损伤标志物与较低的神经认知T评分相关（p<0.01）。此外，血浆血管细胞黏附分子-1与神经丝轻链相关（r=0.29，p=0.003）。生物标志物聚类将HAND分为三个聚类：两个聚类血管疾病患病率高，血管细胞黏附分子-1和神经丝轻链升高，炎症谱独特（C反应蛋白/细胞间黏附分子-1/YKL-40或白细胞介素-6/白细胞介素-8/白细胞介素-15/单核细胞趋化蛋白-1），一个聚类没有明显的生物标志物升高。
在接受抑制性ART的HIV感染者中，血管损伤标志物比炎症标志物与HAND和CNS损伤的关系更密切，可能有助于区分VCI对HAND的相对贡献。
