Benlarbi Mehdi, Richard Jonathan, Bourassa Catherine, Tolbert William D, Chartrand-Lefebvre Carl, Gendron-Lepage Gabrielle, Sylla Mohamed, El-Far Mohamed, Messier-Peet Marc, Guertin Camille, Turcotte Isabelle, Fromentin Rémi, Verly Myriam Maude, Prévost Jérémie, Clark Andrew, Mothes Walther, Kaufmann Daniel E, Maldarelli Frank, Chomont Nicolas, Bégin Philippe, Tremblay Cécile, Baril Jean-Guy, Trottier Benoit, Trottier Sylvie, Duerr Ralf, Pazgier Marzena, Durand Madeleine, Finzi Andrés
medRxiv. 2023 Aug 16:2023.08.15.23294128. doi: 10.1101/2023.08.15.23294128.
Chronic inflammation persists in some people living with HIV (PLWH), even during antiretroviral therapy (ART) and is associated with premature aging. The gp120 subunit of the HIV-1 envelope glycoprotein can shed from viral and cellular membranes and can be detected in plasma and tissues, showing immunomodulatory properties even in the absence of detectable viremia. We evaluated whether plasmatic soluble gp120 (sgp120) and a family of gp120-specific anti-cluster A antibodies, which were previously linked to CD4 depletion , could contribute to chronic inflammation, immune dysfunction, and sub-clinical cardiovascular disease in participants of the Canadian HIV and Aging cohort (CHACS) with undetectable viremia.
Cross-sectional assessment of plasmatic sgp120 and anti-cluster A antibodies was performed in 386 individuals from CHACS. Their association with pro-inflammatory cytokines, as well as subclinical coronary artery disease measured by computed tomography coronary angiography was assessed using linear regression models.
In individuals with high levels of sgp120, anti-cluster A antibodies inversely correlated with CD4 count (p=0.042) and CD4:CD8 ratio (p=0.004). The presence of sgp120 was associated with increased plasma levels of IL-6. In participants with detectable atherosclerotic plaque and detectable sgp120, sgp120 levels, anti-cluster A antibodies and their combination correlated positively with the total volume of atherosclerotic plaques (p=0.01, 0.018 and 0.006, respectively).
Soluble gp120 may act as a pan toxin causing immune dysfunction and sustained inflammation in a subset of PLWH, contributing to the development of premature comorbidities. Whether drugs targeting sgp120 could mitigate HIV-associated comorbidities in PLWH with suppressed viremia warrants further studies.
Soluble gp120 is detected in the plasma of people living with HIV-1 with undetectable viremia. The presence of soluble gp120 and anti-cluster A antibodies is associated with immune dysfunction, chronic inflammation, and sub-clinical cardiovascular disease.
一些感染艾滋病毒（PLWH）的人即使在接受抗逆转录病毒治疗（ART）期间仍存在慢性炎症，且与早衰有关。HIV-1包膜糖蛋白的gp120亚基可从病毒和细胞膜上脱落，并可在血浆和组织中检测到，即使在没有可检测到的病毒血症的情况下也显示出免疫调节特性。我们评估了血浆可溶性gp120（sgp120）和一组先前与CD4耗竭有关的gp120特异性抗A簇抗体是否会导致加拿大艾滋病毒与衰老队列（CHACS）中病毒血症检测不到的参与者出现慢性炎症、免疫功能障碍和亚临床心血管疾病。
对CHACS的386名个体进行血浆sgp120和抗A簇抗体的横断面评估。使用线性回归模型评估它们与促炎细胞因子以及通过计算机断层扫描冠状动脉造影测量的亚临床冠状动脉疾病之间的关联。
在sgp120水平较高的个体中，抗A簇抗体与CD4计数（p=0.042）和CD4:CD8比值（p=0.004）呈负相关。sgp120的存在与血浆IL-6水平升高有关。在可检测到动脉粥样硬化斑块且可检测到sgp120的参与者中，sgp120水平、抗A簇抗体及其组合与动脉粥样硬化斑块总体积呈正相关（分别为p=0.01、0.018和0.006）。
可溶性gp120可能作为一种泛毒素，在一部分PLWH中导致免疫功能障碍和持续炎症，促使过早出现合并症。针对sgp120的药物是否能减轻病毒血症得到抑制的PLWH中与艾滋病毒相关的合并症，值得进一步研究。
在病毒血症检测不到的HIV-1感染者血浆中检测到可溶性gp120。可溶性gp120和抗A簇抗体的存在与免疫功能障碍、慢性炎症和亚临床心血管疾病有关。
