Frias Miguel A, Pagano Sabrina, Bararpour Nasim, Sidibé Jonathan, Kamau Festus, Fétaud-Lapierre Vanessa, Hudson Peter, Thomas Aurélien, Lecour Sandrine, Strijdom Hans, Vuilleumier Nicolas
Division of Laboratory Medicine, Diagnostic Department, Geneva University Hospitals, Geneva, Switzerland.
Department of Medical Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Front Cardiovasc Med. 2024 Feb 13;11:1343361. doi: 10.3389/fcvm.2024.1343361. eCollection 2024.
This study aimed to study the relationship between auto-antibodies against apolipoprotein A1 (anti-apoA1 IgG), human immunodeficiency virus (HIV) infection, anti-retroviral therapy (ART), and the tryptophan pathways in HIV-related cardiovascular disease.
This case-control study conducted in South Africa consisted of control volunteers ( = 50), people living with HIV (PLWH) on ART ( = 50), and untreated PLWH ( = 44). Cardiovascular risk scores were determined, vascular measures were performed, and an extensive biochemical characterisation (routine, metabolomic, and inflammatory systemic profiles) was performed.
Anti-apoA1 IgG levels were assessed by an in-house ELISA. Inflammatory biomarkers were measured with the Meso Scale Discovery® platform, and kynurenine pathway metabolites were assessed using targeted metabolomic profiling conducted by liquid chromatography-multiple reaction monitoring/mass spectrometry (LC-MRM/MS).
Cardiovascular risk scores and vascular measures exhibited similarities across the three groups, while important differences were observed in systemic inflammatory and tryptophan pathways. Anti-apoA1 IgG seropositivity rates were 15%, 40%, and 70% in control volunteers, PLWH ART-treated, and PLWH ART-naïve, respectively. Circulating anti-apoA1 IgG levels were significantly negatively associated with CD4+ cell counts and positively associated with viremia and pro-inflammatory biomarkers (IFNγ, TNFα, MIPα, ICAM-1, VCAM-1). While circulating anti-apoA1 IgG levels were associated with increased levels of kynurenine in both control volunteers and PLWH, the kynurenine/tryptophan ratio was significantly increased in PLWH ART-treated.
HIV infection increases the humoral response against apoA1, which is associated with established HIV severity criteria and kynurenine pathway activation.
本研究旨在探讨抗载脂蛋白A1自身抗体（抗载脂蛋白A1 IgG）、人类免疫缺陷病毒（HIV）感染、抗逆转录病毒疗法（ART）与HIV相关心血管疾病中色氨酸代谢途径之间的关系。
这项在南非进行的病例对照研究包括对照志愿者（n = 50）、接受ART治疗的HIV感染者（PLWH，n = 50）和未接受治疗的PLWH（n = 44）。测定心血管风险评分，进行血管测量，并进行广泛的生化特征分析（常规、代谢组学和炎症系统谱）。
采用内部酶联免疫吸附测定法（ELISA）评估抗载脂蛋白A1 IgG水平。使用Meso Scale Discovery®平台测量炎症生物标志物，并通过液相色谱-多反应监测/质谱法（LC-MRM/MS）进行靶向代谢组学分析来评估犬尿氨酸途径代谢物。
三组的心血管风险评分和血管测量结果相似，但在全身炎症和色氨酸途径方面观察到重要差异。对照志愿者、接受ART治疗的PLWH和未接受ART治疗的PLWH中抗载脂蛋白A1 IgG血清阳性率分别为15%、40%和70%。循环抗载脂蛋白A1 IgG水平与CD4 +细胞计数显著负相关，与病毒血症和促炎生物标志物（IFNγ、TNFα、MIPα、ICAM-1、VCAM-1）正相关。虽然在对照志愿者和PLWH中循环抗载脂蛋白A1 IgG水平均与犬尿氨酸水平升高有关，但接受ART治疗的PLWH中犬尿氨酸/色氨酸比值显著升高。
HIV感染会增加针对载脂蛋白A1的体液反应，这与既定的HIV严重程度标准和犬尿氨酸途径激活有关。
