Swanta Naomi, Aryal Subhash, Nejtek Vicki, Shenoy Sangeeta, Ghorpade Anuja, Borgmann Kathleen
Department of Microbiology, Immunology and Genetics, Graduate School of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, TX, USA.
Department of Biostatistics, School of Public Health, University of North Texas Health Science Center, Fort Worth, TX, USA.
J Neurovirol. 2020 Jun;26(3):358-370. doi: 10.1007/s13365-020-00834-3. Epub 2020 Mar 19.
Inflammation in people living with HIV (PLWH) correlates with severity of HIV-associated neurocognitive disorders. The objective of this study is to identify blood-based markers of neurocognitive function in a demographic balanced cohort of PLWH. Seven neurocognitive domains were evaluated in 121 seropositive Black/African American, Non-Hispanic White, and White Hispanic men and women using computerized assessments. Associations among standardized neurocognitive function and HIV-related parameters, relevant sociodemographic variables, and inflammation-associated cytokines measured in plasma and cellular supernatants were examined using multivariate and univariate regression models. Outlier and covariate analyses were used to identify and normalize for education level, CD4 T cell count, viral load, CNS and drug abuse comorbidities, which could influence biomarker and neurocognitive function associations. Plasma levels of chemokine (C-C motif) ligand (CCL) 8 significantly associated with memory, complex attention, cognitive flexibility, psychomotor speed, executive function, and processing speed. Plasma tissue inhibitor of metalloproteinases 1 associated with the aforementioned domains except memory and processing speed. In addition, plasma interleukin-23 significantly associated with processing speed and executive function. Analysis of peripheral blood cell culture supernatants revealed no significant markers for neurocognitive function. In this cohort, CD4 T cell count and education level also significantly associated with neurocognitive function. All identified inflammatory biomarkers demonstrated a negative correlation to neurocognitive function. These cytokines have known connections to HIV pathophysiology and are potential biomarkers for neurocognitive function in PLWH with promising clinical applications.
人类免疫缺陷病毒感染者（PLWH）的炎症与HIV相关神经认知障碍的严重程度相关。本研究的目的是在一个人口统计学均衡的PLWH队列中确定基于血液的神经认知功能标志物。使用计算机化评估对121名血清阳性的黑人/非裔美国人、非西班牙裔白人以及西班牙裔白人男性和女性的七个神经认知领域进行了评估。使用多变量和单变量回归模型检查了标准化神经认知功能与HIV相关参数、相关社会人口统计学变量以及血浆和细胞上清液中测量的炎症相关细胞因子之间的关联。使用异常值和协变量分析来识别并对教育水平、CD4 T细胞计数、病毒载量、中枢神经系统和药物滥用合并症进行标准化，这些因素可能会影响生物标志物与神经认知功能的关联。趋化因子（C-C基序）配体（CCL）8的血浆水平与记忆、复杂注意力、认知灵活性、精神运动速度、执行功能和处理速度显著相关。金属蛋白酶组织抑制剂1的血浆水平与上述领域相关，但与记忆和处理速度无关。此外，血浆白细胞介素-23与处理速度和执行功能显著相关。外周血细胞培养上清液分析未发现神经认知功能的显著标志物。在这个队列中，CD4 T细胞计数和教育水平也与神经认知功能显著相关。所有确定的炎症生物标志物均与神经认知功能呈负相关。这些细胞因子与HIV病理生理学已知存在关联，并且是PLWH神经认知功能的潜在生物标志物，具有良好的临床应用前景。
