Department of Obstetrics and Gynecology, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing, Jiangsu, China.
Front Immunol. 2024 Oct 10;15:1461767. doi: 10.3389/fimmu.2024.1461767. eCollection 2024.
To investigate the features of HBV-specific T cell reactivity across the pregnant, postpartum or non-pregnant women with chronic HBV infection.
A total of 283 patients with chronic HBV infection were enrolled in this study, including 129 patients during pregnancy, 58 patients during postpartum less than 6 months and 96 non-pregnant patients at childbearing age. A universal ELISpot assay was set up using a broad-spectrum T-cell epitope peptide library which containing 103 functionally validated CD8 T-cell epitopes derived from overall HBsAg, HBc/eAg, HBx and HBpol proteins and fitting to the human leukocyte antigen polymorphisms of Chinese population. Then, The functional HBV-specific T cells in peripheral blood were detected.
The spot-forming units (SFUs) of HBV-specific T cells in the pregnant group showed no statistical difference from the postpartum group, but significantly less than that in the non-pregnant group (p = 0.046). In the untreated patients, the pregnant group displayed HBe/cAg-specific T cells (SFUs) less than the non-pregnant group ( = 0.025) and the postpartum group ( = 0.045). Meanwhile, in the NUCs-treated patients, the three groups presented similar HBV-specific T cell reactivity. Furthermore, the SFUs in the NUCs-treated pregnant group were similar to that in the NUCs-untreated pregnant group. Importantly, ROC analysis demonstrated that the HBV-specific T cells (SFUs) (AUC = 0.742) and combined with HBsAg levels (AUC = 0.775) or with HBeAg level (AUC = 0.78) had a good predictive performance for hepatitis progression during pregnancy group.
Pregnancy can reduce HBV-specific T cell reactivity in the women with chronic HBV infection, and NUCs treatment cannot improve their HBV-specific T cells reactivity. Routine monitoring of HBV-specific T cells during pregnant and postpartum period can provide precise evaluation for immune function and valuable guidance for treatments.
研究慢性乙型肝炎病毒（HBV）感染孕妇、产后及非孕期女性的 HBV 特异性 T 细胞反应特征。
本研究共纳入 283 例慢性 HBV 感染者，包括 129 例妊娠期、58 例产后 6 个月内及 96 例育龄期非孕期患者。采用广谱 T 细胞表位肽库建立通用 ELISpot 检测，该肽库包含 103 个源自 HBsAg、HBc/eAg、HBx 和 HBpol 蛋白的功能验证的 CD8 T 细胞表位，适用于中国人群的人类白细胞抗原多态性。然后，检测外周血中的功能性 HBV 特异性 T 细胞。
与非孕期组相比，妊娠期组 HBV 特异性 T 细胞的斑点形成单位（SFU）无统计学差异，但显著低于产后组（p = 0.046）。在未治疗的患者中，与非孕期组（p = 0.025）和产后组（p = 0.045）相比，妊娠期组 HBe/cAg 特异性 T 细胞（SFU）减少。同时，在 NUCs 治疗组中，三组均表现出相似的 HBV 特异性 T 细胞反应。此外，NUCs 治疗的妊娠组的 SFU 与未治疗的妊娠组相似。重要的是，ROC 分析表明，HBV 特异性 T 细胞（SFU）（AUC = 0.742）和联合 HBsAg 水平（AUC = 0.775）或 HBeAg 水平（AUC = 0.78）对预测妊娠期间乙型肝炎进展具有良好的预测性能。
妊娠可降低慢性 HBV 感染女性的 HBV 特异性 T 细胞反应，NUCs 治疗不能改善其 HBV 特异性 T 细胞反应。在妊娠和产后期间常规监测 HBV 特异性 T 细胞可对免疫功能进行精确评估，并为治疗提供有价值的指导。
