HBV母婴传播致新生儿免疫失败的原因和机制

目的:了解新生儿HBV免疫失败与宫内HBV感染,外周血单个核细胞(PBMC)中HBV DNA及其与白细胞介素2(IL-2)的相互关系,探讨HBV母婴传播致新生儿免疫失败的原因和内在机制.方法:52例HbsAg阳性无症状携带孕妇及其新生儿作为实验组,8例HBV M阴性孕妇及其新生儿作为正常对照组.用巢式联合酶链反应(Nested-PCR)技术检测新生儿血清和PBMC中HBV DNA,固相放射免疫法检测血清乙型肝炎病毒抗原抗体(HBV M),采用体外细胞培养和双抗体夹心酶联合免疫法检测PBMC在植物素(PHA)和HBsAg刺激下,培养上清液中IL-2的含量.结果:HBsAg阳性母亲新生儿,PBMC中HBV DNA阳性者免疫接种失败率明显高于PBMC中HBV DNA阴性者,有显著差异性(P＜0.01).PHA或HBsAg刺激下,HBsAg阳性孕妇分娩的新生儿中,PBMC中HBV DNA阳性者PBMC培养上清液中IL-2含量明显低于PBMC中HBV DNA阴性者和正常对照组新生儿,差异均有显著性(P＜0.01).而后两者比较,差异无显著性(P＞0.05).PHA或HBsAg刺激下,免疫接种失败新生儿PBMC培养上清液中IL-2含量明显低于免疫接种成功新生儿和正常对照组新生儿,差异均有显著性(P＜0.01).而后两者比较,差异无显著性(P＞0.05).结论:宫内感染HBV并侵犯PBMC,是新生儿免疫接种失败的重要原因;HBV侵犯PBMC可使其IL-2分泌能力下降,可能是导致新生儿免疫接种失败的机制之一.

Causes and mechanisms of immunization failure in newborns deduced by maternal-fetal hepatitis B virus (HBV) from transmission

AIM: To study the relationships between newborns' immunization failure and intrauterine infection, peripheral blood mononuclear cells (PBMC) and interleukin 2(IL-2) and to explore the reasons and mechanisms of immunization failure in newborns induced by maternal-fetal BHV transmission. METHODS: Fifty-two pregnant women carrying HBsAg but with no symptoms and their newborns were taken as the experiential group, while 8 pregnant women with HBV M negative and their newborns as the normal control group. The newborns' serum and PBMC HBV DNA were detected by Nested-PCR and HBV M was tested with solid phase radioimmunoassay. PBMC from the newborns were incubated by PHA and HBsAg and the supernatant IL-2 level was measured by enzyme linked immununosorbent assay (ELISA). RESULTS: In the newborns born from HbsAg positive mothers, the immunization failure percentage was obviously higher in HBV DNA positive PBMC than that in HBV DNA negative PBMC, and there was significant difference between them ( P <0.01). Under the stimulation of PHA or HBsAg in the newborns from HbsAg positive mothers, the IL-2 levels in PBMC supernatant were obviously lower in HBV DNA positive PBMC group than those in HBV DNA negative and normal control groups. Significant difference was found between the former and the latter two( P <0.01) while no difference was found between the latter two ( P >0.05). Under the stimulation of PHA or HBsAg, the IL-2 levels in PBMC supernatant were obviously lower in vaccination failure newborns than those in vaccination success and normal control groups. There was significant difference between the former and the latter two ( P <0.01) but no difference was found between the latter two ( P > 0.05). CONCLUSION: The interuterine PBMC HBV invasion is one of the important causes of vaccination failure in the newborns. The down-regulation of PBMC IL-2 autocrine is closely related to the HBV invasion, which may lead to the failure of HBVac inoculation in the newborns.