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在接受预防性抗病毒干预的HBeAg阳性孕妇中,PgRNA与细胞因子谱密切相关。

PgRNA closely correlates to cytokine profile in HBeAg-positive pregnant women undergoing prophylactic antiviral intervention.

作者信息

Tang Qiao, Wang Chunrui, Li Hu, Chen Zhiwei, Liu Xiaoqing, Xue Yunling, Qiu Yue, Zeng Yi, Hu Peng

机构信息

The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

出版信息

Front Immunol. 2024 Dec 11;15:1511855. doi: 10.3389/fimmu.2024.1511855. eCollection 2024.

Abstract

BACKGROUND

Previous studies primarily focused on the effects of ALT and virology, but there is a lack of research on the correlations of HBcrAg and pgRNA, two novel virologic markers, with immunological parameters in pregnant women with CHB undergoing prophylactic antiviral intervention.

METHODS

We conducted a retrospective cohort study involving 28 HBeAg-positive pregnant women with CHB undergoing prophylactic antiviral intervention. Clinical data, virological markers (HBV DNA, HBsAg, HBeAg, HBcrAg and pgRNA) and 28 cytokines were detected at three time points: 24-28 weeks gestation (before prophylactic antiviral intervention), near birth and within 3 months postpartum.

RESULTS

PgRNA was moderately (correlation coefficient between 0.4 and 0.6) positively correlated with Th1-type cytokines (IFN-γ, IL12p70, IL2, and TNF-α), Th17-type cytokines (IL21), Th2-type cytokines (IL10, IL4, and IL5), and cytokines regulating cell proliferation and differentiation (CTLA4, IL15, IL23, and TGF-β1) and moderately negatively correlated with EGF (correlation coefficient = -0.4), while ALT, HBV-DNA, HBsAg and HBcrAg were insignificantly correlated with cytokines at 24-28 weeks of gestation. Most cytokines tended to be elevated, with statistically significant increases observed only for the chemokines IP10 and MCP-1 during pregnancy. Most cytokines were significantly increased in postpartum women with virologic rebound after treatment discontinuation postpartum, but no significant change in the Th1/Th2 ratio. Changes in virologic markers were significantly correlated with cytokines. Immune activation was more pronounced in postpartum women who developed ALT flare compared to who did not, with Th1-type cytokines (especially IL12p40) and chemokines being main differential cytokines.

CONCLUSION

PgRNA was more closely correlated with cytokine profiles, and postpartum ALT flare may be the result of the interaction between Th1-type cytokines and chemokines.

摘要

背景

既往研究主要聚焦于丙氨酸氨基转移酶(ALT)和病毒学效应,但缺乏关于乙肝核心抗原(HBcrAg)和前基因组RNA(pgRNA)这两种新型病毒学标志物与接受预防性抗病毒干预的慢性乙型肝炎(CHB)孕妇免疫参数相关性的研究。

方法

我们进行了一项回顾性队列研究,纳入28例接受预防性抗病毒干预的HBeAg阳性CHB孕妇。在妊娠24 - 28周(预防性抗病毒干预前)、临产前和产后3个月这三个时间点检测临床数据、病毒学标志物(乙肝病毒DNA、乙肝表面抗原、HBeAg、HBcrAg和pgRNA)以及28种细胞因子。

结果

PgRNA与Th1型细胞因子(干扰素-γ、白细胞介素12p70、白细胞介素2和肿瘤坏死因子-α)、Th17型细胞因子(白细胞介素21)、Th2型细胞因子(白细胞介素10、白细胞介素4和白细胞介素5)以及调节细胞增殖和分化的细胞因子(细胞毒性T淋巴细胞相关抗原4、白细胞介素15、白细胞介素23和转化生长因子-β1)呈中度正相关(相关系数在0.4至0.6之间),与表皮生长因子(EGF)呈中度负相关(相关系数 = -0.4),而在妊娠24 - 28周时,ALT、乙肝病毒DNA、乙肝表面抗原和HBcrAg与细胞因子的相关性不显著。大多数细胞因子有升高趋势,孕期仅趋化因子IP10和单核细胞趋化蛋白-1有统计学意义的升高。产后停药出现病毒学反弹的女性中,大多数细胞因子显著升高,但Th1/Th2比值无显著变化。病毒学标志物的变化与细胞因子显著相关。与未出现ALT波动的产后女性相比,出现ALT波动的产后女性免疫激活更明显,Th1型细胞因子(尤其是白细胞介素12p40)和趋化因子是主要的差异细胞因子。

结论

PgRNA与细胞因子谱的相关性更强,产后ALT波动可能是Th1型细胞因子与趋化因子相互作用的结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46d2/11668345/73a273492218/fimmu-15-1511855-g001.jpg

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