新生儿脐血细胞因子Elafin、IL-18、IFN-γ/IL-4与HBV宫内感染的相关性研究

The relationship of elafin, IL-18, and IFN-γ/IL-4 ratio in the cord blood of neonates with HBV intrauterine infection

摘要:

目的 研究新生儿脐血细胞因子弹性蛋白酶特异性抑制物（Elafin）、白细胞介素18（IL-18）、γ-干扰素（IFN-γ）/白细胞介素4（IL-4）与乙型肝炎病毒（HBV）宫内感染的相关性。方法 选取2016年5月—2019年5月攀枝花市妇幼保健院收治的HBV携带产妇分娩的新生儿96例。其中，31例发生HBV宫内感染新生儿作为宫内感染组，65例未感染新生儿作为宫内未感染组。另选取同期该院非HBV携带且健康产妇分娩的新生儿90例作为对照组。比较3组脐血Elafin、IL-18、IFN-γ、IL-4水平及IFN-γ/IL-4，分析新生儿宫内感染影响因素、脐血因子之间关联性及与HBV-DNA载量相关性。结果 宫内感染组Elafin、IL-18、IFN-γ、IFN-γ/IL-4低于宫内未感染组、对照组，IL-4高于宫内未感染组、对照组（P <0.05）。宫内感染组与宫内未感染者组产妇HBV大三阳、羊水情况、阴道流血史的比较，差异有统计学意义（P <0.05）。产妇HBV大三阳［R=3.125（95% CI：2.379，4.105），P<0.05］、产妇羊水浑浊［R=2.781（95% CI：2.041，3.790），P <0.05］、产妇阴道流血史［R=2.389（95% CI：1.816，3.144），P <0.05］、Elafin［R=0.574（95% CI：0.405，0.813），P <0.05］、IL-18［R=0.529（95% CI：0.352，0.796），P <0.05］、IFN-γ/IL-4［R=0.475（95% CI：0.440，0.512），P <0.05］是新生儿HBV宫内感染的影响因素。Elafin与IL-18呈正相关（r =0.649，P <0.05），IFN-γ/IL-4与Elafin、IL-18呈正相关（r =0.529和0.499，P <0.05）。HBV-DNA载量≥ 1.00×10⁴copies/ml患者Elafin、IL-18、IFN-γ/IL-4 水平较< 1.00×10⁴copies/ml患者低（P <0.05）。Elafin、IL-18、IFN-γ/IL-4与HBV-DNA载量呈负相关（r =-0.601、-0.556和-0.712，均P <0.05）。结论 Elafin、IL-18、IFN-γ/IL-4在新生儿宫内感染中呈异常表达，并与HBV-DNA载量密切相关。

Abstract:

Objective To investigate the relationship of elafin, interleukin-18 (IL-18), and γ-interferon (IFN-γ)/IL-4 ratio in the cord blood of neonates with intrauterine infection of hepatitis B virus (HBV).Methods Ninety-six neonates born to mothers who were carriers of HBV from May 2016 to May 2019 in our hospital were selected as observation group. Among them, 31 cases suffered from HBV intrauterine infection. In addition, 90 healthy neonates born to mothers who were not carriers of HBV during the same period were enrolled as the control group. The levels of elafin, IL-18, IFN-γ, IL-4 and IFN-γ/IL-4 ratio in umbilical cord blood of the three groups were compared, and the correlation among these factors and their relationship with HBV-DNA load as well as the influencing factors for HBV intrauterine infection were analyzed.Results The levels of elafin, IL-18, IFN-γ, and IFN-γ/IL-4 ratio were lower, but IL-4 level was higher in the cord blood of the neonates with intrauterine infection born to mothers who were carriers of HBV compared with the neonates without intrauterine infection born to mothers who were carriers of HBV and healthy neonates born to mothers who were not carriers of HBV (P < 0.05). The incidence of maternal combined positive hepatitis B surface antigen, hepatitis B e-antigen and hepatitis B core antibody, amniotic fluid turbidity, and history of vaginal bleeding was different between the neonates with and without intrauterine infection born to mothers who were carriers of HBV (P < 0.05). Being born to mothers with combined positive hepatitis B surface antigen, hepatitis B e-antigen and hepatitis B core antibody [R=3.125 (95% CI: 2.379, 4.105), P < 0.05], amniotic fluid turbidity [R=2.781 (95% CI: 2.041, 3.790), P < 0.05], and a history of vaginal bleeding [R=2.389 (95% CI: 1.816, 3.144), P < 0.05], as well as the levels of elafin [R=0.574 (95% CI: 0.405, 0.813), P < 0.05], IL-18 [R=0.529 (95% CI: 0.352, 0.796), P < 0.05], and IFN-γ/IL-4 ratio [R=0.475 (95% CI: 0.440, 0.512), P < 0.05] in the cord blood were essential influencing factors for neonatal HBV intrauterine infection (P < 0.05). The level of elafin in the cord blood was positively correlated with that of IL-8 (r = 0.649, P < 0.05), and IFN-γ/IL-4 ratio was also positively correlated with the level of elafin and IL-18 (r = 0.529 and 0.499, P < 0.05). Those with HBV-DNA load ≥104 copies/ml had lower levels of elafin, IL-18, and IFN-γ/IL-4 ratio compared with those with HBV-DNA load <104 copies/ml (P < 0.05). The levels of elafin, IL-18 and IFN-γ/IL-4 ratio were negatively correlated with HBV-DNA load (r = -0.601, -0.556 and -0.712, all P < 0.05).Conclusions The levels of elafin, IL-18, and IFN-γ/IL-4 ratio in the cord blood are abnormal in neonates with HBV intrauterine infection, and are closely related to HBV-DNA load.