GUT｜复旦大学陈捷亮/张敏/袁正宏/张继明教授共同通信研究发现功能性抗-preS1抗体应答与慢性乙型肝炎病毒控制密切相关

乙型肝炎病毒（HBV）大表面蛋白的preS1抗原在病毒感染入胞环节发挥关键作用，但关于HBV慢性感染中preS1抗原及抗-preS1抗体的表达情况及其功能意义，尚缺乏系统研究。

肽P9~P11的氨基酸序列为AFGANSNNPDWDFNPNKDTWPDA，其中AFGANSNNPDWDF片段位于preS1与NTCP隧道区结合的界面，NPNKDTWPDA片段位于preS1与NTCP表面结合的界面。

近日，复旦大学陈捷亮、张敏、袁正宏、张继明团队以共同通讯作者身份，在Gut（IF=41.111）发表最新研究论著，系统揭示了：慢性乙型肝炎（CHB）患者血清 preS1 抗原水平与 HBV DNA、HBsAg 及 HBeAg 呈显著正相关；而抗 - preS1 IgG 抗体水平与 HBV DNA 呈显著负相关，且在部分功能性治愈患者中可持续检出。进一步功能实验显示，preS1 抗原低表达、抗 - preS1 IgG 高滴度的患者血清，可有效阻断 preS1 与肝细胞受体 NTCP 的结合，展现出强效 HBV/HDV 中和活性；抗 - preS1 抗体所识别的线性表位，主要富集于 preS1 与 NTCP 结合的关键功能界面。在核苷（酸）类似物（NUC）停药队列中，基线高水平抗 - preS1 抗体与停药后持续病毒学抑制显著相关，提示其可作为预测 CHB 功能性治愈与停药安全性的重要免疫学标志物。

图：核苷（酸）类似物停药后慢性乙型肝炎患者基线血清抗前S1 IgG水平及其对病毒学复发的预测效能。

综上，该研究系统阐明了慢性乙型肝炎感染状态下 preS1 抗原与抗 - preS1 抗体的表达规律及其潜在临床价值：功能性抗 - preS1 抗体应答可介导机体实现病毒控制，有助于核苷（酸）类似物（NUC）停药后维持持续性病毒学抑制。该研究进一步丰富并深化了人们对慢性乙型肝炎抗病毒免疫应答机制的理解，同时明确了抗 - preS1 抗体在患者病毒学风险分层、个体化 HBsAg 特异性免疫状态评估方面的重要应用前景。

https://gut.bmj.com/content/early/2026/06/22/gutjnl-2025-337810

Title：Functional anti-preS1 antibody responses associated with viral control in chronic hepatitis BAbstract

BackgroundThe preS1 region of the HBV large surface protein binds sodium taurocholate cotransporting polypeptide (NTCP) to mediate viral entry, but the serological and functional relevance of circulating preS1 antigen and anti-preS1 antibodies in chronic hepatitis B (CHB) is not well defined.

ObjectiveTo characterise serum preS1 antigen and anti-preS1 IgG across CHB and evaluate their virological and functional significance.

DesignELISAs for preS1 antigen and anti-preS1 IgG were developed and applied to 549 individuals with chronic HBV infection, 107 individuals with functional cureand 110 vaccinated healthy controls. Neutralising activity was assessed using HBV and hepatitis D virus (HDV) infection models, preS1-NTCP competitive assays and peptide microarrays. Baseline anti-preS1 IgG was evaluated in 51 patients discontinuing nucleos(t)ide analogue (NUC) therapy.

ResultsPreS1 antigen was highest in hepatitis B e antigen (HBeAg)-positive patients and correlated with HBV DNA, hepatitis B surface antigen and HBeAg. Anti-preS1 IgG was detectable across disease phases, inversely associated with HBV DNA, positively correlated with alanine aminotransferase/aspartate aminotransferase and remained detectable in some individuals with functional cure. Sera with low preS1 and high anti-preS1 IgG showed potent HBV/HDV neutralising activity by inhibiting viral entry and blocking preS1-NTCP binding. Dominant linear epitopes mapped to preS1 regions involved in NTCP binding. High baseline anti-preS1 IgG was associated with sustained virological suppression after NUC withdrawal.

ConclusionPreS1 antigenaemia and anti-preS1 IgG exhibit distinct serological patterns linked to HBV replication and endogenous viral control. High anti-preS1 IgG confers potential neutralising activity and associates with sustained off-therapy suppression, highlighting its functional relevance as an indicator of host viral control.

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