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乙型肝炎病毒感染及母婴传播阻断策略对母婴 T 细胞免疫的影响。

Effects of hepatitis B virus infection and strategies for preventing mother-to-child transmission on maternal and fetal T-cell immunity.

机构信息

Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

Department of Obstetrics and Gynecology, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Front Immunol. 2023 Feb 16;14:1122048. doi: 10.3389/fimmu.2023.1122048. eCollection 2023.

Abstract

One of the most common routes of chronic hepatitis B virus (HBV) infection is mother-to-child transmission (MTCT). Approximately 6.4 million children under the age of five have chronic HBV infections worldwide. HBV DNA high level, HBeAg positivity, placental barrier failure, and immaturity of the fetal immune are the possible causes of chronic HBV infection. The passive-active immune program for children, which consists of the hepatitis B vaccine and hepatitis B immunoglobulin, and antiviral therapy for pregnant women who have a high HBV DNA load (greater than 2 × 10 IU/ml), are currently two of the most important ways to prevent the transmission of HBV from mother to child. Unfortunately, some infants still have chronic HBV infections. Some studies have also found that some supplementation during pregnancy can increase cytokine levels and then affect the level of HBsAb in infants. For example, IL-4 can mediate the beneficial effect on infants' HBsAb levels when maternal folic acid supplementation. In addition, new research has indicated that HBV infection in the mother may also be linked to unfavorable outcomes such as gestational diabetes mellitus, intrahepatic cholestasis of pregnancy, and premature rupture of membranes. The changes in the immune environment during pregnancy and the hepatotropic nature of HBV may be the main reasons for the adverse maternal outcomes. It is interesting to note that after delivery, the women who had a chronic HBV infection may spontaneously achieve HBeAg seroconversion and HBsAg seroclearance. The maternal and fetal T-cell immunity in HBV infection is important because adaptive immune responses, especially virus-specific CD8 T-cell responses, are largely responsible for viral clearance and disease pathogenesis during HBV infection. Meanwhile, HBV humoral and T-cell responses are important for the durability of protection after fetal vaccination. This article reviews the literature on immunological characteristics of chronic HBV-infected patients during pregnancy and postpartum, blocking mother-to-child transmissions and related immune mechanisms, hoping to provide new insights for the prevention of HBV MTCT and antiviral intervention during pregnancy and postpartum.

摘要

慢性乙型肝炎病毒(HBV)感染的最常见途径之一是母婴传播(MTCT)。全球约有 640 万 5 岁以下儿童患有慢性 HBV 感染。HBV DNA 高水平、HBeAg 阳性、胎盘屏障失效和胎儿免疫不成熟是慢性 HBV 感染的可能原因。目前,预防 HBV 母婴传播的两种最重要方法是儿童的被动-主动免疫方案,包括乙型肝炎疫苗和乙型肝炎免疫球蛋白,以及对 HBV DNA 载量高(大于 2×10 IU/ml)的孕妇进行抗病毒治疗。不幸的是,一些婴儿仍然患有慢性 HBV 感染。一些研究还发现,怀孕期间的某些补充剂可以增加细胞因子水平,从而影响婴儿的 HBsAb 水平。例如,IL-4 可以介导母体叶酸补充对婴儿 HBsAb 水平的有益影响。此外,新的研究表明,母亲的 HBV 感染也可能与不良结局相关,如妊娠期糖尿病、妊娠肝内胆汁淤积症和胎膜早破。怀孕期间免疫环境的变化和 HBV 的嗜肝性可能是导致不良母婴结局的主要原因。有趣的是,分娩后,患有慢性 HBV 感染的女性可能会自发地实现 HBeAg 血清学转换和 HBsAg 血清学清除。HBV 感染中的母婴 T 细胞免疫很重要,因为适应性免疫反应,特别是病毒特异性 CD8 T 细胞反应,在很大程度上负责 HBV 感染期间的病毒清除和疾病发病机制。同时,HBV 体液和 T 细胞反应对于胎儿接种后的保护持久性很重要。本文综述了慢性 HBV 感染患者在妊娠和产后的免疫特征、阻断母婴传播和相关免疫机制的文献,希望为预防 HBV MTCT 和妊娠及产后抗病毒干预提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7e7/9978148/7032e42440c0/fimmu-14-1122048-g001.jpg

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