Department of Infectious Diseases, The Alfred and Monash University, Level 2, Burnet Institute, 85 Commercial Road, Melbourne, VIC 3004, Australia; Burnet Institute, 85 Commercial Road, Melbourne, VIC 3004, Australia.
Department of Infectious Diseases, The Alfred and Monash University, Level 2, Burnet Institute, 85 Commercial Road, Melbourne, VIC 3004, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Level 6, The Alfred Centre (Alfred Hospital), 99 Commercial Road, Melbourne, VIC 3004, Australia.
EBioMedicine. 2017 Aug;22:112-121. doi: 10.1016/j.ebiom.2017.07.015. Epub 2017 Jul 18.
Chronic immune activation persists despite antiretroviral therapy (ART) in HIV+ individuals and underpins an increased risk of age-related co-morbidities. We assessed the Frailty Index in older HIV+ Australian men on ART. Immunometabolic markers on monocytes and T cells were analyzed using flow cytometry, plasma innate immune activation markers by ELISA, and lipidomic profiling by mass spectrometry. The study population consisted of 80 HIV+ men with a median age of 59 (IQR, 56-65), and most had an undetectable viral load (92%). 24% were frail, and 76% were non-frail. Frailty was associated with elevated Glucose transporter-1 (Glut1) expression on the total monocytes (p=0.04), increased plasma levels of innate immune activation marker sCD163 (OR, 4.8; CI 1.4-15.9, p=0.01), phosphatidylethanolamine PE(36:3) (OR, 5.1; CI 1.7-15.5, p=0.004) and triacylglycerol TG(16:1_18:1_18:1) (OR, 3.4; CI 1.3-9.2, p=0.02), but decreased expression of GM3 ganglioside, GM3(d18:1/18:0) (OR, 0.1; CI 0.0-0.6, p=0.01) and monohexosylceramide HexCerd(d18:1/22:0) (OR, 0.1; CI 0.0-0.5, p=0.004). There is a strong inverse correlation between quality of life and the concentration of PE(36:3) (ρ=-0.33, p=0.004) and PE(36:4) (ρ=-0.37, p=0.001). These data suggest that frailty is associated with increased innate immune activation and abnormal lipidomic profile. These markers should be investigated in larger, longitudinal studies to determine their potential as biomarkers for frailty.
慢性免疫激活在接受抗逆转录病毒疗法 (ART) 的 HIV+个体中持续存在，并且增加了与年龄相关的合并症的风险。我们评估了接受 ART 的老年 HIV+澳大利亚男性的虚弱指数。使用流式细胞术分析单核细胞和 T 细胞的免疫代谢标志物，通过 ELISA 分析血浆固有免疫激活标志物，通过质谱分析脂质组学特征。研究人群包括 80 名中位年龄为 59 岁（IQR，56-65）的 HIV+男性，大多数人的病毒载量无法检测到（92%）。24%的人虚弱，76%的人不虚弱。虚弱与总单核细胞上葡萄糖转运蛋白-1（Glut1）表达升高（p=0.04）、血浆固有免疫激活标志物 sCD163 水平升高（OR，4.8；95%CI，1.4-15.9，p=0.01）、磷酸乙醇胺 PE(36:3)（OR，5.1；95%CI，1.7-15.5，p=0.004）和三酰甘油 TG(16:1_18:1_18:1)（OR，3.4；95%CI，1.3-9.2，p=0.02）有关，但 GM3 神经节苷脂 GM3(d18:1/18:0)（OR，0.1；95%CI，0.0-0.6，p=0.01）和单半乳糖基神经酰胺 HexCerd(d18:1/22:0)（OR，0.1；95%CI，0.0-0.5，p=0.004）的表达降低。生活质量与 PE(36:3)（ρ=-0.33，p=0.004）和 PE(36:4)（ρ=-0.37，p=0.001）的浓度之间存在很强的负相关。这些数据表明，虚弱与固有免疫激活增加和脂质组学谱异常有关。这些标志物应在更大的纵向研究中进行研究，以确定它们作为虚弱标志物的潜力。
