文章摘要
严敏,邵昱璋,王海荣,胡妮,付婷,高洁,张磊.HBsAg阳性产妇IL-18的表达在HBV宫内传播中的相关性研究[J].中华流行病学杂志,2019,40(9):1071-1076
HBsAg阳性产妇IL-18的表达在HBV宫内传播中的相关性研究
Correlation study of IL-18 expression in HBsAg positive parturients in intrauterine transmission of HBV
投稿时间:2019-02-01  
DOI:10.3760/cma.j.issn.0254-6450.2019.09.010
中文关键词: 乙型肝炎病毒;宫内传播;显性感染;隐匿性感染;白介素18
英文关键词: HBV;Intrauterine transmission;Dominate infection;Occult infection;Interleukin 18
基金项目:国家自然科学基金(81102140,81472988,81773488);国家重点研发计划(2016YFC1303204);陕西省自然科学基础研究(2018JM7109097)
作者单位E-mail
严敏 空军军医大学军事预防医学系流行病学教研室 特殊作业环境危害评估与防治教育部重点实验室, 西安 710032  
邵昱璋 西安交通大学医学院 710061  
王海荣 空军军医大学军事预防医学系流行病学教研室 特殊作业环境危害评估与防治教育部重点实验室, 西安 710032  
胡妮 空军军医大学军事预防医学系流行病学教研室 特殊作业环境危害评估与防治教育部重点实验室, 西安 710032  
付婷 空军军医大学军事预防医学系流行病学教研室 特殊作业环境危害评估与防治教育部重点实验室, 西安 710032  
高洁 空军军医大学军事预防医学系流行病学教研室 特殊作业环境危害评估与防治教育部重点实验室, 西安 710032  
张磊 空军军医大学军事预防医学系流行病学教研室 特殊作业环境危害评估与防治教育部重点实验室, 西安 710032 drzhanglei@fmmu.edu.cn 
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中文摘要:
      目的 探讨HBsAg阳性产妇外周血白介素18(IL-18)水平在HBV宫内传播(BIT)中的表达变化。方法 采用病例对照研究,以陕西省西北妇女儿童医院住院分娩的282例HBsAg阳性产妇为病例组,43例健康产妇为对照组进行流行病学调查,采用ELISA法检测孕妇和新生儿外周血乙型肝炎(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IL-18水平。结果 HBsAg阳性产妇发生HBV宫内显性感染(DBI)率、HBV宫内隐匿性感染(OBI)率、BIT率分别为8.42%(24/285)、40.00%(114/285)和48.42%(138/285)。对照产妇的IL-18水平显著低于HBsAg阳性产妇组(P=0.001)、宫内未传播(NBIT)组(P=0.001)、OBI组(P<0.001);HBeAg阴性组IL-18水平显著低于HBeAg阳性组(P=0.023);产妇HBV DNA载量≥103拷贝/ml,其IL-18水平显著高于对照组(P<0.01),并随着母血中HBV DNA载量的增高,其IL-18水平呈增高趋势(P=0.024),当HBV DNA载量在103~106拷贝/ml,其DBI组IL-18水平显著低于NBIT组(P=0.022),并随着BIT程度的加重,其IL-18水平呈下降趋势(P=0.016);未接种乙肝疫苗组中呈现随着BIT程度的加重,其IL-18含量明显减少的趋势(P=0.044),未接种乙肝疫苗和乙肝免疫球蛋白组中,OBI组IL-18水平均显著高于NBIT组(P<0.05);多因素分析结果显示,产妇HBeAg与母体IL-18水平的线性关系有统计学意义(P=0.01)。结论 IL-18是Th1/Th2网络平衡更高层次的调控者,监测HBsAg阳性孕妇体内IL-18水平,不仅可以对其新生儿发生DBI和OBI进行预判,而且可以考虑作为干预手段,尤其对于HBeAg阳性和HBV DNA载量≥103拷贝/ml者,提高母体的细胞免疫功能,从而有利于控制BIT。
英文摘要:
      Objective To investigate the expression of IL-18 in peripheral blood of HBsAg positive parturients in intrauterine transmission of 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, real time PCR was used to detect HBV DNA, and flow liquid chip method was used to detect IL-18 levels in peripheral blood of parturients and newborns. Results The incidence of dominant HBV infection (DBI), occult HBV infection (OBI) and intrauterine transmission of HBV were 8.42% (24/285), 40.00% (114/285) and 48.42% (138/285), respectively. The level of IL-18 in peripheral blood of HBsAg-negative parturients were significantly lower than those of HBsAg-positive parturients (P=0.001), non-HBV intrauterine transmission (NBIT) group (P=0.001) and OBI group (P<0.001). The level of IL-18 in HBeAg negative group was significantly lower than that in HBeAg positive group (P=0.023). When HBV DNA load was ≥ 103 copies/ml, the level of IL-18 was significantly higher than that in HBsAg-negative group (P<0.01). With the increase of HBV DNA load in maternal blood, the level of IL-18 increased (P=0.024). When HBV DNA load was 103-106 copies/ml, the level of IL-18 in DBI group was significantly lower than that in NBIT group (P=0.022), and increased with the increase of HBV DNA load in maternal blood (P=0.016). With the increased severity of intrauterine transmission of HBV, the level of IL-18 in non-hepatitis B vaccine group decreased significantly (P=0.044). The level of IL-18 in non-hepatitis B vaccine group and immunoglobulin injection group was significantly higher than that in NBIT group (P<0.05). Multivariate analysis showed that the linear relationship between maternal HBeAg status and maternal IL-18 levels had statistical significance (P=0.01). Conclusions IL-18 is a higher level balance regulator of Th1/Th2 immune network. Monitoring the level of IL-18 in HBsAg-positive parturients can be used not only for predicting the probability of DBI and OBI, but also as an intervention mean, especially for those who are HBeAg-positive and had HBV DNA load ≥ 103 copies/ml, to improve maternal cellular immune function, which is conducive to interrupting intrauterine transmission and providing a theoretical basis for the prevention and control of HBV intrauterine transmission.
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