Labuschagne Naidoo Robyn-Brooke, Steel Helen C, Theron Annette J, Anderson Ronald, Tintinger Gregory R, Rossouw Theresa M
Department of Internal Medicine, School of Medicine, Faculty of Health Sciences, University of Pretoria and Steve Biko Academic Hospital, Pretoria 0002, South Africa.
Department of Immunology, School of Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria 0002, South Africa.
Pathogens. 2024 Jun 27;13(7):540. doi: 10.3390/pathogens13070540.
Increasing drug resistance and the absence of a cure necessitates exploration of novel treatment strategies for people living with HIV (PLWH). Targeting of soluble co-inhibitory immune checkpoint molecules (sICMs) represents a novel, potentially effective strategy in the management of HIV.
In this retrospective, longitudinal, observational study, the plasma levels of five prominent co-inhibitory sICMs-CTLA-4, LAG-3, PD-1 and its ligand PD-L1, as well as TIM-3-were quantified in 68 PLWH-before and one year after antiretroviral therapy (ART)-and compared with those of 15 healthy control participants.
Relative to control participants, PLWH had substantially elevated pre-treatment levels of all five co-inhibitory sICMs ( < 0.0001- < 0.0657), which, over the 12-month period of ART, remained significantly higher than those of controls ( < 0.0367- < 0.0001). PLWH with advanced disease, reflected by a CD4+ T cell count <200 cells/mm before ART, had the lowest levels of CTLA-4 and LAG-3, while participants with pre-treatment HIV viral loads ≥100,000 copies/mL had higher pre-treatment levels of TIM-3, which also persisted at 12 months.
Plasma levels of CTLA-4, LAG-3, PD-1, PD-L1 and TIM-3 were significantly elevated in treatment-naïve PLWH and remained so following one year of virally-suppressive ART, possibly identifying LAG-3 and TIM-3 in particular as potential targets for adjuvant immunotherapy.
耐药性增加且尚无治愈方法，因此有必要探索针对人类免疫缺陷病毒感染者（PLWH）的新型治疗策略。靶向可溶性共抑制免疫检查点分子（sICM）是管理HIV的一种新型潜在有效策略。
在这项回顾性、纵向观察性研究中，对68名PLWH在抗逆转录病毒治疗（ART）前及治疗一年后的血浆中五种主要共抑制sICM——细胞毒性T淋巴细胞相关蛋白4（CTLA-4）、淋巴细胞活化基因3蛋白（LAG-3）、程序性死亡受体1（PD-1）及其配体程序性死亡配体1（PD-L1）以及T细胞免疫球蛋白黏蛋白分子3（TIM-3）的水平进行了定量，并与15名健康对照参与者的水平进行比较。
与对照参与者相比，PLWH在治疗前所有五种共抑制sICM的水平均大幅升高（<0.0001-<0.0657），在ART的12个月期间，这些水平仍显著高于对照组（<0.0367-<0.0001）。ART前CD4+T细胞计数<200个细胞/mm³反映的疾病进展期PLWH，其CTLA-4和LAG-3水平最低，而治疗前HIV病毒载量≥100,000拷贝/mL的参与者TIM-3治疗前水平较高，在12个月时也持续存在。
初治PLWH的血浆CTLA-4、LAG-3、PD-1、PD-L1和TIM-3水平显著升高，在进行一年病毒抑制性ART后仍保持如此，这可能表明特别是LAG-3和TIM-3是辅助免疫治疗的潜在靶点。
