HBsAg阳性产妇孕晚期IFN-γ和IL-12表达对HBV宫内传播的影响

张磊; 王海荣; 邵昱璋; 严敏; 付婷; 胡妮; 高洁

Abstract

张磊,王海荣,邵昱璋,严敏,付婷,胡妮,高洁.HBsAg阳性产妇孕晚期IFN-γ和IL-12表达对HBV宫内传播的影响[J].Chinese journal of Epidemiology,2019,40(9):1077-1083

HBsAg阳性产妇孕晚期IFN-γ和IL-12表达对HBV宫内传播的影响

Effect of IFN-γ and IL-12 expressions on intrauterine transmission in HBsAg-positive parturientsin late pregnancy

Received:February 18, 2019

DOI：10.3760/cma.j.issn.0254-6450.2019.09.011

KeyWord: 乙型肝炎病毒显性感染隐匿性感染 γ干扰素白介素12

English Key Word: HBV Dominate infection Occult infection IFN-γ IL-12

FundProject:国家自然科学基金（81102140，81472988，81773488）；陕西省重点研发计划（2018SF-166）；陕西省自然科学基础研究（2018JM7109097）

Author Name	Affiliation	E-mail
Zhang Lei	Department of Epidemiology, Key Laboratory of Hazard Assessment and Control in Special Operational Environment of Ministry of Education, School of Military Preventive Medicine, Air Force Military Medical University, Xi'an 710032, China	drzhanglei@fmmu.edu.cn
Wang Hairong	Department of Epidemiology, Key Laboratory of Hazard Assessment and Control in Special Operational Environment of Ministry of Education, School of Military Preventive Medicine, Air Force Military Medical University, Xi'an 710032, China
Shao Yuzhang	Medical College, Xi'an Jiaotong University, Xi'an 710061, China
Yan Min	Department of Epidemiology, Key Laboratory of Hazard Assessment and Control in Special Operational Environment of Ministry of Education, School of Military Preventive Medicine, Air Force Military Medical University, Xi'an 710032, China
Fu Ting	Department of Epidemiology, Key Laboratory of Hazard Assessment and Control in Special Operational Environment of Ministry of Education, School of Military Preventive Medicine, Air Force Military Medical University, Xi'an 710032, China
Hu Ni	Department of Epidemiology, Key Laboratory of Hazard Assessment and Control in Special Operational Environment of Ministry of Education, School of Military Preventive Medicine, Air Force Military Medical University, Xi'an 710032, China
Gao Jie	Department of Epidemiology, Key Laboratory of Hazard Assessment and Control in Special Operational Environment of Ministry of Education, School of Military Preventive Medicine, Air Force Military Medical University, Xi'an 710032, China

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Abstract:

目的探讨HBsAg阳性产妇外周血IFN-γ和IL-12水平对HBV在宫内传播（BIT）中的影响。方法采用病例对照研究，连续收集2015年1月至2017年5月陕西省西北妇女儿童医院分娩的282例HBsAg阳性产妇为病例组，以43例健康产妇为对照组进行流行病学调查，采用ELISA法检测临产前产妇的外周血乙型肝炎（乙肝）五项指标，采用实时荧光定量PCR检测HBV DNA水平，采用流式液相芯片法检测细胞因子IFN-γ和IL-12水平；对其所生285例新生儿于产后24 h内静脉血进行乙肝五项和HBV DNA水平检测。结果 HBsAg阳性产妇人群发生HBV宫内显性感染（DBI）率、HBV宫内隐匿性感染（OBI）率、BIT率分别为7.37%（21/285）、40.70%（116/285）和48.07%（137/285）。对照组IFN-γ水平显著低于HBsAg阳性产妇组（t=-2.55，P=0.011）、NBIT组（t=-2.54，P=0.012）和OBI组（t=-2.33，P=0.021），对照组中IL-12水平显著高于NBIT组（t=2.07，P=0.040）和DBI组（t=4.81，P=0.000）；对照组IL-12水平显著高于HBsAg阳性产妇的HBeAg阴性组（t=-2.09，P=0.038）；HBV DNA载量在10³～10⁶拷贝/ml组中DBI组IFN-γ水平显著低于OBI组和NBIT组（P<0.01）；注射免疫球蛋白组中随着BIT程度的加重，其IFN-γ含量明显减少（χ²=6.40，P=0.041），抗病毒治疗组中随着BIT程度的加重，其IL-12含量明显减少（χ²=8.90，P=0.012）；产妇年龄、前置胎盘和乙肝疫苗注射与母体IFN-γ水平的线性关系有统计学意义（P<0.05），破膜方式和乙肝疫苗注射与母体IL-12水平的线性关系有统计学意义（P<0.05）。结论 HBV可以激发孕产妇体内IFN-γ的表达，同时抑制IL-12的分泌，但是IFN-γ在HBsAg阳性产妇体内的表达呈现组内分化现象，在HBeAg阳性和高载量HBV DNA的环境下母体IFN-γ的水平会下降；提高HBsAg阳性产妇的IFN-γ和IL-12水平，有利于阻断BIT尤其是DBI。

English Abstract:

Objective To investigate the influence of IFN-γ and IL-12 levels in prenatal peripheral blood of HBsAg-positive parturients on intrauterine transmission of hepatitis B virus (HBV). Methods A case-control study was conducted in 282 HBsAg positive parturients and 43 health parturients (control group) in Northwest Women and Children Hospital of Shaanxi Province. Enzyme-linked immunosorbent assay (ELISA) was used to detect five serological makers of hepatitis B in peripheral blood of parturients. HBV DNA was detected by real-time fluorescence quantitative PCR. Detection of cytokines IFN-γ and IL-12 levels were conducted with liquid chip-based flow cytometry method. The serum levels of five serological markers of hepatitis B and HBV DNA in 285 newborns were detected within 24 hours after birth. Results The incidence of intrauterine dominant infection (DBI), occult infection (OBI) and intrauterine transmission of HBV in HBsAg positive parturients were 7.37% (21/285), 40.70% (116/285) and 48.07% (137/285), respectively. The level of IFN-γ in peripheral blood of HBsAg-negative parturients was significantly lower than those of HBsAg-positive parturients (t=-2.55, P=0.011), NBIT group (t=-2.54, P=0.012) and OBI group (t=-2.33, P=0.021). In HBV DNA load of 10³-10⁶ copies/ml group, the levels of IFN-γ in the DBI group were significantly lower than those in OBI group and NBIT group (P<0.01). The level of IFN-γ in maternal peripheral blood decreased significantly with the increased severity of intrauterine transmission of HBV (χ²=6.40, P=0.041). In the antiviral treatment group, the level of IL-12 in maternal peripheral blood decreased significantly with the increased severity of intrauterine transmission of HBV (χ²=8.90, P=0.012). Multivariate analysis showed that there was a significant linear relationship between maternal IFN-γ level and maternal age, placenta previa and hepatitis B vaccine injection (P<0.05). The linear relationship between the level of maternal IL-12 and the mode of rupture and hepatitis B vaccine injection had statistical significance (P<0.05). Conclusions HBV can stimulate the expression of IFN-γ and inhibit the secretion of IL-12 in pregnant and lying-in women, but the expression of IFN-γ in HBsAg-positive parturients showed intra-group differentiation, and the maternal level of IFN-γ will decrease in HBeAg-positive and high-HBV DNA loadstatus. Increasing the levels of IFN-γ and IL-12 in HBsAg-positive parturients is beneficial to block intrauterine transmission of HBV, especially DBI.

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