| 姚添,扆琳珠,王科科,李雁笛,渠轶群,丰淑英,王素萍,冯永亮.HBsAg阳性母亲新生儿干扰素基因刺激因子天然免疫信号通路对婴儿乙型肝炎疫苗无/弱应答的影响[J].Chinese journal of Epidemiology,2023,44(9):1447-1453 |
| HBsAg阳性母亲新生儿干扰素基因刺激因子天然免疫信号通路对婴儿乙型肝炎疫苗无/弱应答的影响 |
| Effects of neonatal stimulator of interferon genes innate immune signaling pathway of HBsAg-positive mothers on non/hypo-response to hepatitis B vaccine in infants |
| Received:July 15, 2023 |
| DOI：10.3760/cma.j.cn112338-20230715-00005 |
| KeyWord: 干扰素基因刺激因子 信号通路 乙型肝炎疫苗 无/弱应答 婴儿 |
| English Key Word: Stimulator of interferon genes Signal pathway Hepatitis B vaccine Non/hypo-response Infant |
| FundProject:国家自然科学基金（81872677，82073622）；山西省基础研究计划（202203021212353）；山西医科大学第一医院博士启动基金（YB2201） |
| Author Name | Affiliation | E-mail | | Yao Tian | The First Clinical Medical College of Shanxi Medical University, Taiyuan 030001, China
Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan 030001, China | | | Yi Linzhu | Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan 030001, China
Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China | | | Wang Keke | The First Hospital of Shanxi Medical University, Taiyuan 030001, China | | | Li Yandi | Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan 030001, China
Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China | | | Qu Yiqun | Department of Obstetrics and Gynaecology, The Third People's Hospital of Taiyuan, Taiyuan 030001, China | | | Feng Shuying | Department of Obstetrics and Gynaecology, The Third People's Hospital of Taiyuan, Taiyuan 030001, China | | | Wang Suping | Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan 030001, China
Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China | | | Feng Yongliang | Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan 030001, China
Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China | yongliang.feng@sxmu.edu.cn |
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| Abstract: |
| 目的 探讨HBsAg阳性母亲新生儿干扰素基因刺激因子（STING）天然免疫信号通路对婴儿乙型肝炎（乙肝）疫苗无/弱应答的影响。方法 选取2019年11月至2022年6月在太原市第三人民医院分娩的HBsAg阳性母亲及其新生儿/婴儿作为研究对象，采用问卷调查和病历查阅的方式收集其流行病学资料和临床资料，运用流式细胞术检测新生儿脐血中STING天然免疫信号通路关键分子蛋白（STING、pIRF3）以及疫苗应答相关免疫细胞（DC、T、B和浆细胞）。对全程规范接种乙肝疫苗后1~2个月的婴儿进行随访，通过化学发光微粒子免疫分析法检测随访婴儿血清抗-HBs。结合非条件logistic回归模型、列线图和贝叶斯网络模型探讨STING天然免疫信号通路和相关因素在婴儿乙肝疫苗无/弱应答中的作用与贡献大小，以及各因素间相互关系。结果 共调查195对HBsAg阳性母亲及其婴儿，婴儿乙肝疫苗无/弱应答率为12.31%（24/195）。母亲HBV DNA高载量、新生儿STING蛋白低表达、pIRF3蛋白低表达和浆细胞低表达是婴儿乙肝疫苗无/弱应答的危险因素（OR值分别为4.70、3.46、3.18和2.20，均P<0.05），以上因素构建的列线图具有良好的预测效能（曲线下面积=0.81，95%CI：0.63~0.83）。贝叶斯网络模型结果显示，母亲HBV DNA高载量时，新生儿STING蛋白低表达的条件概率较高（62.50%），其pIRF3蛋白低表达的条件概率较高（58.54%），DC、T、B和浆细胞低表达的条件概率均较高（53.16%、60.20%、68.42%和57.14%）。结论 母亲HBV DNA可能通过抑制其新生儿STING天然免疫信号通路及疫苗应答相关免疫细胞导致婴儿乙肝疫苗无/弱应答。 |
| English Abstract: |
| Objective To explore the effects of neonatal stimulator of interferon genes (STING) innate immune signaling pathway of HBsAg-positive mothers on non/hypo-response to hepatitis B vaccine (HepB) in their infants. Methods From November 2019 to June 2022, HBsAg-positive mothers and their infants in the Third People's Hospital of Taiyuan were recruited as the study subjects. The epidemiological and clinical data were collected by questionnaire survey and medical records review. The key molecular proteins of STING innate immune signaling pathway (STING, pIRF3) and immune cells associated with vaccine response (DC, T and B and plasma cells) in neonatal cord blood were detected by flow cytometry. Follow up was conducted for infants for 1-2 months after the full vaccination of HepB. Serum hepatitis B surface antibody (anti-HBs) was detected by chemiluminescence microparticle immunoassay. Unconditional logistic regression model, nomogram and Bayesian network model were used to evaluate the effect of STING innate immune signaling pathway on non/hypo-response to HepB and related factors in infants, and the relationship between various factors. Results A total of 195 pairs of HBsAg-positive mothers and infants were recruited, the rate of non/hypo-response to HepB in the infants was 12.31% (24/195). High maternal HBV DNA load, low expression of neonatal STING, low expression of pIRF3 and low percentage of plasma cells were risk factors for non/hypo-response to HepB in the infants (OR=4.70, 3.46, 3.18 and 2.20, all P<0.05). The nomogram constructed by these factors had good predictive efficacy (area under curve=0.81, 95%CI:0.63-0.83). The results of Bayesian network model showed that the infants with a high maternal HBV DNA load had a higher conditional probability of low STING expression (62.50%) and a higher conditional probability of low pIRF3 expression (58.54%). The conditional probabilities of low expression of DC, T, B and plasma cells were 53.16%, 60.20%, 68.42% and 57.14%, respectively. Conclusion Maternal HBV DNA might inhibit STING innate immune signaling pathways in infants and immune cells associated with HepB response, resulting in non/hypo-response to HepB in infants of HBsAg-positive mothers. |
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