The Immunology Laboratory of the Biotechnology Center, University of Yaoundé I, Yaounde, Cameroon.
Department of Animals Biology and Physiology of the Faculty of Sciences, University of Yaoundé I, Yaoundé, Cameroon.
Front Immunol. 2023 Sep 18;14:1216480. doi: 10.3389/fimmu.2023.1216480. eCollection 2023.
Human Herpesvirus-8 (HHV-8) is the etiologic agent of Kaposi's sarcoma (KS), a multicentric angio-proliferative cancer commonly associated with Human Immunodeficiency Virus (HIV) infection. KS pathogenesis is a multifactorial condition hinged on immune dysfunction yet the mechanisms underlying the risk of developing KS in HHV-8 seropositive adults remains unclear. Here we explored whether soluble markers of HIV-1-related systemic immune activation (SIA) and angiogenesis (VEGF and FGF acidic) are involved in the pathogenesis of KS in adults with HHV8.
Blood samples from 99 HIV-1 infected and 60 HIV-1 uninfected adults were collected in Yaoundé, Cameroon. CD3+/CD4+ T cell counts and HIV-1 plasma viral load were determined using the Pima Analyzer and the RT-PCR technique, respectively. Plasma levels of SIA biomarkers (sCD163, sCD25/IL-2Rα, and sCD40/TNFRSF5) and biomarkers of progression to KS (VEGF and FGF acidic) were measured using the Luminex assay. Seropositivity (IgG) for HHV-8 was determined using the ELISA method.
Overall, 20.2% (20/99) of HIV-1 infected and 20% (12/60) of HIV-1 uninfected participants were seropositive for HHV8. Levels of sCD163, sCD25/IL-2Rα, sCD40/TNFRSF5, and FGF acidic were higher in the HIV-1 and HHV8 co-infection groups compared to the HIV-1 and HHV8 uninfected groups (all P <0.05). In addition, Higher plasma levels of VEGF correlated with sCD163 (r = 0.58, P =0.0067) and sCD40/TNFRSF5 (r = 0.59, P = 0.0064), while FGF acidic levels correlated with sCD40/TNFRSF5 (r = 0.51, P = 0.022) in co-infected. In HIV-1 mono-infected donors, VEGF and FGF acidic levels correlated with sCD163 (r =0.25, P = 0.03 and r = 0.30, P = 0.006 respectively), sCD25/IL-2Rα (r = 0.5, P <0.0001 and r = 0.55, P <0.0001 respectively) and sCD40/TNFRSF5 (r = 0.7, P <0.0001 and r = 0.59, P <0.0001 respectively) and even in patients that were virally suppressed sCD25/IL-2Rα (r = 0.39, P = 0.012 and r = 0.53, P = 0.0004 respectively) and sCD40/TNFRSF5 (r = 0.81, P <0.0001 and r = 0.44, P = 0.0045 respectively).
Our findings suggest that although the development of KS in PLWH is multifactorial, HIV-associated SIA might be among the key drivers in coinfections with HHV8 and is independent of the patients' viremic status.
人类疱疹病毒 8 型（HHV-8）是卡波西肉瘤（KS）的病原体，KS 是一种常见于人类免疫缺陷病毒（HIV）感染的多中心血管增生性癌症。KS 的发病机制是一种多因素的疾病，取决于免疫功能障碍，但 HHV-8 血清阳性成年人中发生 KS 的风险的机制仍不清楚。在这里，我们探讨了 HIV-1 相关全身免疫激活（SIA）和血管生成（VEGF 和 FGF 酸性）的可溶性标志物是否参与了 HHV8 成人的 KS 发病机制。
在喀麦隆雅温得收集了 99 名 HIV-1 感染和 60 名 HIV-1 未感染的成年人的血液样本。使用 Pima 分析仪和 RT-PCR 技术分别测定 CD3+/CD4+T 细胞计数和 HIV-1 血浆病毒载量。使用 Luminex 测定法测量 SIA 生物标志物（sCD163、sCD25/IL-2Rα 和 sCD40/TNFRSF5）和进展为 KS 的生物标志物（VEGF 和 FGF 酸性）的血浆水平。使用 ELISA 法确定 HHV-8 的血清阳性（IgG）。
总体而言，20.2%（20/99）的 HIV-1 感染和 20%（12/60）的 HIV-1 未感染参与者对 HHV8 呈血清阳性。与 HIV-1 和 HHV8 未感染组相比，HIV-1 和 HHV8 共感染组的 sCD163、sCD25/IL-2Rα、sCD40/TNFRSF5 和 FGF 酸性水平更高（均 P <0.05）。此外，较高的 VEGF 血浆水平与 sCD163（r = 0.58，P = 0.0067）和 sCD40/TNFRSF5（r = 0.59，P = 0.0064）相关，而 FGF 酸性水平与 sCD40/TNFRSF5（r = 0.51，P = 0.022）相关在共感染中。在 HIV-1 单感染供体中，VEGF 和 FGF 酸性水平与 sCD163（r = 0.25，P = 0.03 和 r = 0.30，P = 0.006 分别）、sCD25/IL-2Rα（r = 0.5，P <0.0001 和 r = 0.55，P <0.0001 分别）和 sCD40/TNFRSF5（r = 0.7，P <0.0001 和 r = 0.59，P <0.0001 分别）相关，甚至在病毒抑制的患者中，sCD25/IL-2Rα（r = 0.39，P = 0.012 和 r = 0.53，P = 0.0004 分别）和 sCD40/TNFRSF5（r = 0.81，P <0.0001 和 r = 0.44，P = 0.0045 分别）。
我们的研究结果表明，尽管 PLWH 中 KS 的发生是多因素的，但 HIV 相关的 SIA 可能是 HHV8 共感染的关键驱动因素之一，且与患者的病毒血症状态无关。
