Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Aging (Albany NY). 2021 Oct 11;13(19):22772-22791. doi: 10.18632/aging.203625.
Anti-retroviral therapy (ART) improves life expectancy in people living with HIV (PWH), but it remains unclear how chronic HIV infection affects normal aging of the immune system. Plasma cell-free protein expression and immune phenotypes were assessed in blood from ART treated PWH (19-77yrs, = 106) and age-matched, HIV-negative controls (HC, = 103). Using univariate spearman correlation, we identified 277 and 491 age-associated parameters out of a total 1,357 in HC and PWH, respectively. PWH exhibited shared and distinct age-associated immune profiles compared to HC highlighting the effect of HIV infection on immunological aging. Our analysis resulted in an 8-parameter, plasma-detectable inflammatory index that correlated with chronological age of all study participants but was higher overall in PWH. Additionally, predictive modeling for age in HC participants and age-associated parameters generated a 25-parameter signature, IMAP-25, with 70% and 53% accuracy in HC and PWH, respectively. Applying the IMAP-25 signature to immunological data from PWH revealed accelerated aging in PWH by 5.6 yrs. Overall, our results demonstrate that immune signatures, easily monitored in human blood samples, can be used as an indicator of one's 'immunological age' during ART-treated HIV infection and can be applied to other disease states that affect the immune system.
抗逆转录病毒疗法（ART）可提高艾滋病毒感染者（PWH）的预期寿命，但尚不清楚慢性 HIV 感染如何影响免疫系统的正常衰老。从接受 ART 治疗的 PWH（19-77 岁，n = 106）和年龄匹配的 HIV 阴性对照者（HC，n = 103）的血液中评估无浆细胞游离蛋白表达和免疫表型。使用单变量 spearman 相关性分析，我们分别在 HC 和 PWH 中确定了 277 和 491 个与年龄相关的参数，总数为 1357 个。与 HC 相比，PWH 表现出与年龄相关的共同和独特免疫特征，突出了 HIV 感染对免疫衰老的影响。我们的分析得出了一个 8 个参数的、可在血浆中检测到的炎症指数，该指数与所有研究参与者的实际年龄相关，但在 PWH 中总体较高。此外，对 HC 参与者的年龄预测建模和与年龄相关的参数生成了一个 25-参数特征，即 IMAP-25，在 HC 和 PWH 中的准确性分别为 70%和 53%。将 IMAP-25 特征应用于 PWH 的免疫数据，发现 PWH 的免疫衰老速度加快了 5.6 年。总体而言，我们的结果表明，易于在人类血液样本中监测的免疫特征可作为接受 ART 治疗的 HIV 感染期间个体“免疫年龄”的指标，也可应用于影响免疫系统的其他疾病状态。
