Plasma Metabolic Signature and Abnormalities in HIV-Infected Individuals on Long-Term Successful Antiretroviral Therapy
Plasma Metabolic Signature and Abnormalities in HIV-Infected Individuals on Long-Term Successful Antiretroviral Therapy
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DOI：
10.3390/metabo9100210
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发表时间：
2019-10-01
期刊：
影响因子：
4.1
通讯作者：
Neogi, Ujjwal
中科院分区：
文献类型：
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作者：
Babu, Hemalatha;Sperk, Maike;Neogi, Ujjwal
靶向代谢组学研究报告了治疗和未治疗的人类免疫缺陷病毒（HIV）（PLHIV）感染者的代谢异常。本研究旨在了解血浆代谢组学变化，并预测在病例对照研究中长期抑制性抗逆转录病毒治疗（ART）的PLHIV加速老化的风险及其与炎症和神经缺陷的血浆蛋白质组学生物标志物的相关性。从成功长期ART超过五年的PLHIV（n = 22）和匹配的HIV阴性健康个体（n = 22，本文HC）获得血浆样品。使用超高效液相色谱/质谱/质谱（UHPLC/MS/MS）进行非靶向代谢物分析。使用靶向184种血浆蛋白的邻近延伸测定法进行血浆蛋白质组学分析。共250种代谢产物在PLHIV和HC之间存在显著差异（p < 0.05，q < 0.1）。血浆中几种必需氨基酸的水平，除了组氨酸，支链氨基酸和芳香族氨基酸（苯丙氨酸，酪氨酸，色氨酸）显着低于PLHIV相比，HC。对代谢物变化的机器学习预测表明，PLHIV感染者患炎症和神经系统疾病的风险更高。在氨基酸水平、能量学、磷脂和复合脂质中观察到代谢异常，这可能反映了PLHIV中脂蛋白水平的已知差异，类似于代谢综合征（MetS）。
Targeted metabolomics studies reported metabolic abnormalities in both treated and untreated people living with human immunodeficiency virus (HIV) (PLHIV). The present study aimed to understand the plasma metabolomic changes and predicted the risk of accelerated aging in PLHIV on long-term suppressive antiretroviral therapy (ART) in a case-control study setting and its association with the plasma proteomics biomarkers of inflammation and neurological defects. Plasma samples were obtained from PLHIV on successful long-term ART for more than five years (n = 22) and matched HIV-negative healthy individuals (n = 22, HC herein). Untargeted metabolite profiling was carried out using ultra-high-performance liquid chromatography/mass spectrometry/mass spectrometry (UHPLC/MS/MS). Plasma proteomics profiling was performed using proximity extension assay targeting 184 plasma proteins. A total of 250 metabolites differed significantly (p < 0.05, q < 0.1) between PLHIV and HC. Plasma levels of several essential amino acids except for histidine, branched-chain amino acids, and aromatic amino acids (phenylalanine, tyrosine, tryptophan) were significantly lower in PLHIV compared to HC. Machine-learning prediction of metabolite changes indicated a higher risk of inflammatory and neurological diseases in PLHIV. Metabolic abnormalities were observed in amino-acid levels, energetics, and phospholipids and complex lipids, which may reflect known differences in lipoprotein levels in PLHIV that can resemble metabolic syndrome (MetS).