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

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HBVDNA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HBVDNA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HBVDNA载量的增高,其IL-18水平呈增高趋势(P=0.024),当HBVDNA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HBVDNA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。

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.