Garcia-Broncano Pilar, Medrano Luz Maria, Berenguer Juan, González-García Juan, Jiménez-Sousa Mª Ángeles, Carrero Ana, Hontañón Victor, Guardiola Josep M, Crespo Manuel, Quereda Carmen, Sanz José, García-Gómez Ana Belen, Jimenez Jose Luis, Resino Salvador
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Viral Infection and Immunity Unit, National Center of Microbiology, Health Institute Carlos III, 28220 Madrid, Spain.
Cells. 2018 Nov 2;7(11):196. doi: 10.3390/cells7110196.
Advanced cirrhosis is related to alterations in immunity. We aimed to evaluate the levels of peripheral CD4⁺ T cells (Tregs) and plasma cytokine in patients coinfected with human immunodeficiency virus and hepatitis C virus (HIV/HCV) according to liver fibrosis stages [evaluated as liver stiffness measure (LSM)] and their linear relationship.
We performed a cross-sectional study on 238 HIV/HCV-coinfected patients (119 had <12.5 kPa, 73 had 12.5⁻25 kPa, and 46 had >25 kPa). Peripheral T-cell subsets were phenotyped by flow cytometry, plasma biomarkers were assessed by multiplex immunoassays, and LSM was assessed by transient elastography. Results We found HIV/HCV-coinfected patients had higher values of CD4⁺ Tregs ( < 0.001), memory Tregs ( ≤ 0.001), and plasma cytokine levels [IFN-γ ( ≤ 0.05) and IL-10 ( ≤ 0.01)] compared with healthy donors and HIV-monoinfected patients. In the multivariate analysis, higher LSM values were associated with reduced levels of IL-10 (adjusted arithmetic mean ratio (aAMR) = 0.83; = 0.019), IL-2 (aAMR = 0.78; = 0.017), TNF-α (aAMR = 0.67; < 0.001), and IL-17A (aAMR = 0.75; = 0.006). When we focus on HIV/HCV-coinfected patients analyzed by LSM strata, patients with ≥25 kPa had lower values of IL-2 (aAMR = 0.66; = 0.021), TNF-α (aAMR = 0.565; = 0.003), and IL-17A (aAMR = 0.58; = 0.003) than patients with <12.5 kPa.
HIV/HCV-coinfected patients showed an immunosuppressive profile compared to healthy controls and HIV-monoinfected patients. Additionally, HIV/HCV-coinfected patients with advanced cirrhosis (LSM ≥ 25 kPa) had the lowest plasma values of cytokines related to Th1 (IL-2 and TNF-α) and Th17 (IL-17A) response.
晚期肝硬化与免疫功能改变有关。我们旨在根据肝纤维化分期[以肝脏硬度值（LSM）评估]及其线性关系，评估人类免疫缺陷病毒和丙型肝炎病毒合并感染（HIV/HCV）患者外周血CD4⁺调节性T细胞（Tregs）水平和血浆细胞因子水平。
我们对238例HIV/HCV合并感染患者进行了一项横断面研究（119例LSM<12.5 kPa，73例LSM为12.5⁻25 kPa，46例LSM>25 kPa）。通过流式细胞术对外周血T细胞亚群进行表型分析，通过多重免疫测定评估血浆生物标志物，通过瞬时弹性成像评估LSM。结果我们发现，与健康供体和HIV单感染患者相比，HIV/HCV合并感染患者的CD4⁺Tregs（<0.001）、记忆性Tregs（≤0.001）和血浆细胞因子水平[IFN-γ（≤0.05）和IL-10（≤0.01）]更高。在多变量分析中，较高的LSM值与IL-10水平降低相关（校正算术平均比[aAMR]=0.83；P=0.019）、IL-2（aAMR=0.78；P=0.017）、TNF-α（aAMR=0.67；P<0.001）和IL-17A（aAMR=0.75；P=0.006）。当我们关注按LSM分层分析的HIV/HCV合并感染患者时，LSM≥25 kPa的患者与LSM<12.5 kPa的患者相比，IL-2（aAMR=0.66；P=
