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在治疗中,乙型肝炎病毒/人类免疫缺陷病毒合并感染人群中乙型肝炎表面抗原决定的差异 T 细胞谱减少。

Differential T-cell profiles determined by Hepatitis B surface antigen decrease among people with Human Immunodeficiency Virus /Hepatitis B Virus coinfection on treatment.

机构信息

Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.

出版信息

J Transl Med. 2024 Oct 4;22(1):901. doi: 10.1186/s12967-024-05681-y.

Abstract

BACKGROUND

Several studies have reported that combination antiretroviral therapy (cART) enhances the hepatitis B surface antigen (HBsAg) clearance rate in Human Immunodeficiency Virus-1/Hepatitis B Virus (HIV/HBV) coinfected patients, yet the associated immunological characteristics remain unclear.

METHODS

Global and specific immune phenotypic profiles were examined in 48 patients with HIV/HBV coinfection before cART and at 1-year, and 3-year after cART using flow cytometry. In addition, 61 patients with HBV monoinfection were included for comparison.

RESULTS

HBsAg response (sAg-R) was defined as > 0.5 log decrease within six months of cART initiation, and 16 patients achieved it. Patients with sAg-R (the sAg-R group) exhibited distinct immune phenotypes compared to those of HBsAg-retained patients (the sAg-NR group). Notably, patients with sAg-R had lower CD4 T cell counts and a higher number of HBcAg-specific T cells. Further, the sAg-R group exhibited upregulation of HLA-DR, Ki67, and PD-1 in CD4 T cells and heightened HLA-DR and T-bet in CD8 T cells. However, the sAg-R group had fewer TEMRA cells but more TEM and Th17 cells than those in the sAg-NR group. Expression of various markers, including HLA-DRCD4, Ki67CD4, PD-1CD4, CD38CD8, HLA-DRCD8, TIM-3CD8, HBV-specific CD4 T cell secreting IFN-γ and IL-2, and specific CD8 T cell secreting IFN-γ and IL-2, correlated with HBsAg decrease.

CONCLUSION

The decline in HBsAg levels during cART in HIV/HBV coinfection involves significant alterations in CD4 and CD8 T cells phenotypes, offering a novel perspective on a functional HBV cure.

摘要

背景

几项研究报告称,联合抗逆转录病毒疗法(cART)可提高人类免疫缺陷病毒-1/乙型肝炎病毒(HIV/HBV)合并感染患者的乙型肝炎表面抗原(HBsAg)清除率,但相关的免疫特征仍不清楚。

方法

采用流式细胞术检测 48 例 HIV/HBV 合并感染患者 cART 前、cART 后 1 年和 3 年的全免疫和特异性免疫表型谱。此外,还纳入了 61 例 HBV 单感染患者作为对照。

结果

HBsAg 应答(sAg-R)定义为 cART 开始后 6 个月内 HBsAg 下降>0.5 log,有 16 例患者达到这一标准。与 HBsAg 持续存在的患者(sAg-NR 组)相比,sAg-R 患者(sAg-R 组)具有明显不同的免疫表型。值得注意的是,sAg-R 患者的 CD4 T 细胞计数较低,HBcAg 特异性 T 细胞数量较多。此外,sAg-R 组 CD4 T 细胞中 HLA-DR、Ki67 和 PD-1 的表达上调,CD8 T 细胞中 HLA-DR 和 T-bet 的表达上调。然而,sAg-R 组 TEMRA 细胞较少,但 TEM 和 Th17 细胞较多。与 sAg-NR 组相比,sAg-R 组 HLA-DRCD4、Ki67CD4、PD-1CD4、CD38CD8、HLA-DRCD8、TIM-3CD8、HBV 特异性 CD4 T 细胞分泌 IFN-γ 和 IL-2、特异性 CD8 T 细胞分泌 IFN-γ 和 IL-2 的各种标志物的表达与 HBsAg 下降相关。

结论

HIV/HBV 合并感染患者 cART 期间 HBsAg 水平下降涉及 CD4 和 CD8 T 细胞表型的显著改变,为功能性乙型肝炎治愈提供了新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4276/11452968/318b223e0a44/12967_2024_5681_Fig1_HTML.jpg

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