关键词: Antibody subtype HBV Monoclonal antibody Quantitative hepatitis B core antibody T cell Treatment response

来  源:   DOI:10.1016/j.antiviral.2024.105975

Abstract:
BACKGROUND: Hepatitis B core antibody (anti-HBc) is commonly present in patients with chronic hepatitis B virus (HBV) infection and serves as a marker of humoral immunity. Herein, we aim to investigate the correlation between anti-HBc and antiviral immune response and its putative role in HBV control.
METHODS: Quantitative anti-HBc and levels of anti-HBc subtypes were measured in chronic hepatitis B (CHB) patients. The effects of anti-HBc on immune cells and HBV replication were evaluated using the HBV mouse models and human hepatoma cell lines.
RESULTS: Baseline levels of IgG1 and IgG3 anti-HBc were elevated in CHB patients with favorable treatment response, and correlated with the virological response observed at week 52. Additionally, increased levels of IgM and IgG1 anti-HBc were observed exclusively in CHB patients with liver inflammation. Notably, significant correlations were identified between quantitative levels of anti-HBc and the frequencies of HBcAg-specific CD8+ T cells. Intriguingly, HBcAg efficiently activates T cells aided by B cells in vitro experiments. Moreover, anti-HBc inhibits HBV replication either by a direct effect or through complement-mediated cytotoxicity in HBV-producing cell lines.
CONCLUSIONS: Anti-HBc reflects the activation of an HBV-specific CD8+ T cell immune response and may have anti-HBV activity.
摘要:
背景:乙型肝炎核心抗体(抗HBc)通常存在于慢性乙型肝炎病毒(HBV)感染患者中,并作为体液免疫的标志物。在这里,我们的目的是探讨抗-HBc和抗病毒免疫应答之间的相关性及其在HBV控制中的作用。
方法:在慢性乙型肝炎(CHB)患者中测量定量抗HBc和抗HBc亚型水平。使用HBV小鼠模型和人肝癌细胞系评估抗HBc对免疫细胞和HBV复制的影响。
结果:IgG1和IgG3抗-HBc的基线水平在CHB患者中升高,具有良好的治疗反应,并与第52周观察到的病毒学应答相关。此外,IgM和IgG1抗-HBc水平升高仅在CHB患者肝脏炎症中观察到。值得注意的是,抗-HBc的定量水平和HBcAg特异性CD8+T细胞的频率之间存在显著的相关性。有趣的是,在体外实验中,HBcAg有效激活B细胞辅助的T细胞。此外,抗HBc通过直接作用或通过补体介导的细胞毒性在HBV产生细胞系中抑制HBV复制。
结论:抗HBc反映了HBV特异性CD8+T细胞免疫应答的激活,可能具有抗HBV活性。
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