Singh Meera V, Uddin Md Nasir, Vidalle Mae Covacevich, Sutton Karli R, Boodoo Zachary D, Peterson Angelique N, Tyrell Alicia, Brenner Raeann, Tivarus Madalina E, Wang Henry Z, Sahin Bogachan, Zhong Jianhui, Weber Miriam, Wang Lu, Qiu Xing, Maggiwar Sanjay B, Schifitto Giovanni
medRxiv. 2023 Mar 27:2023.03.24.23287660. doi: 10.1101/2023.03.24.23287660.
Despite antiretroviral treatment (cART), people living with HIV (PLWH) are more susceptible to neurocognitive impairment (NCI), probably due to synergistic/additive contribution of traditional cerebrovascular risk factors. Specifically, altered blood brain barrier (BBB) and transmigration of inflammatory monocytes are risk factors for developing cerebral small vessel disease (CSVD). In order to investigate if inflammatory monocytes exacerbate CSVD and cognitive impairment, 110 PLWH on cART and 110 age-, sex- and Reynold’s cardiovascular risk score-matched uninfected individuals were enrolled. Neuropsychological testing, brain magnetic resonance imaging and whole blood analyses to measure platelet-monocyte interaction and monocyte, endothelial activation were performed. Results demonstrated that PLWH exhibited increased levels of platelet-monocyte complexes (PMCs) and higher expression of activation molecules on PMCs. PLWH with CSVD had the poorest cognitive performance and the highest circulating levels of non-classical monocytes which exhibited significant inverse correlation with each other. Furthermore, markers of monocyte and endothelium activation were significantly positively correlated indicating BBB impairment. Our results confirm that interaction with platelets activates and drives monocytes towards an inflammatory phenotype in PLWH. In particular, elevated levels of non-classical monocytes may represent a common pathway to neuroinflammation, CSVD and subsequent cognitive impairment, warranting further longitudinal studies to evaluate responsiveness of this potential biomarker.
尽管接受了抗逆转录病毒治疗（cART），但人类免疫缺陷病毒感染者（PLWH）更容易出现神经认知障碍（NCI），这可能是由于传统脑血管危险因素的协同/累加作用所致。具体而言，血脑屏障（BBB）改变和炎性单核细胞的迁移是发生脑小血管疾病（CSVD）的危险因素。为了研究炎性单核细胞是否会加剧CSVD和认知障碍，招募了110名接受cART治疗的PLWH以及110名年龄、性别和雷诺心血管风险评分相匹配的未感染个体。进行了神经心理学测试、脑磁共振成像以及全血分析，以测量血小板-单核细胞相互作用以及单核细胞、内皮细胞激活情况。结果表明，PLWH的血小板-单核细胞复合物（PMC）水平升高，且PMC上激活分子的表达更高。患有CSVD的PLWH认知表现最差，非经典单核细胞的循环水平最高，二者呈显著负相关。此外，单核细胞和内皮细胞激活标志物呈显著正相关，表明血脑屏障受损。我们的结果证实，在PLWH中，与血小板的相互作用会激活单核细胞并使其趋向炎性表型。特别是，非经典单核细胞水平升高可能是神经炎症、CSVD及随后认知障碍的共同途径，需要进一步进行纵向研究以评估这种潜在生物标志物的反应性。
