Yao T, Yi L Z, Wang K K, Li Y D, Qu Y Q, Feng S Y, Wang S P, Feng Y L
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.
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.
Zhonghua Liu Xing Bing Xue Za Zhi. 2023 Sep 10;44(9):1447-1453. doi: 10.3760/cma.j.cn112338-20230715-00005.
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. 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. 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 (=4.70, 3.46, 3.18 and 2.20, all <0.05). The nomogram constructed by these factors had good predictive efficacy (area under curve=0.81, 95%: 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. 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.
探讨乙肝表面抗原（HBsAg）阳性母亲的新生儿干扰素基因刺激物（STING）天然免疫信号通路对其婴儿乙型肝炎疫苗（HepB）无/低应答的影响。2019年11月至2022年6月，招募太原市第三人民医院的HBsAg阳性母亲及其婴儿作为研究对象。通过问卷调查和病历回顾收集流行病学和临床资料。采用流式细胞术检测新生儿脐血中STING天然免疫信号通路的关键分子蛋白（STING、pIRF3）以及与疫苗应答相关的免疫细胞（DC、T、B和浆细胞）。在婴儿完成HepB全程接种后随访1 - 2个月。采用化学发光微粒子免疫分析法检测血清乙肝表面抗体（抗-HBs）。采用非条件逻辑回归模型、列线图和贝叶斯网络模型评估STING天然免疫信号通路对婴儿HepB无/低应答的影响及相关因素，以及各因素之间的关系。共招募195对HBsAg阳性母亲及其婴儿，婴儿HepB无/低应答率为12.31%（24/195）。母亲高HBV DNA载量、新生儿STING低表达、pIRF3低表达和浆细胞低百分比是婴儿HepB无/低应答的危险因素（比值分别为4.70、3.46、3.18和2.20，均<0.05）。由这些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%：0.63 - 0.83）。贝叶斯网络模型结果显示，母亲HBV DNA载量高的婴儿STING低表达的条件概率较高（62.50%），pIRF3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分别为53.16%、60.20%、68.42%和57.14%。母亲HBV DNA可能抑制婴儿的STING天然免疫信号通路以及与HepB应答相关的免疫细胞，导致HBsAg阳性母亲的婴儿对HepB无/低应答。
