联合免疫失败过程中乙型肝炎病毒S基因突变的母婴配对研究

Paired study on hepatitis B virus S gene mutation in immunoprophylaxis failure to prevent HBV vertical transmission

目的:探讨在当前联合免疫方案下,发生乙肝母婴传播免疫预防失败过程中乙型肝炎病毒(HBV)S基因的突变特征。方法:选择15例分娩免疫失败婴儿的孕妇及其联合免疫前的新生儿和免疫后的7月龄婴儿,将母亲、新生儿和婴儿分别配对,对其外周血中HBV的S基因(包括前S和S)分2个片段进行PCR扩增测序,对比母亲、新生儿及婴儿3组间HBV基因型、前S和S基因突变率及突变位点的不同。结果:(1)新生儿和婴儿体内HBV的基因型与母亲完全相同。(2)3组2个片段的突变率差异均无统计学意义(P>0.05);同源树簇集分析中,母亲与所分娩的新生儿和婴儿体内HBV均形成各自独立的簇集。(3)突变位点:母亲-新生儿(13对):7例新生儿与母亲体内的HBV存在不同的突变位点(共15个位点);新生儿-婴儿(13对):3例婴儿与新生儿体内的HBV存在不同的突变位点,即nt273A→A/G、nt512C→C/T和nt1139C→A(共3个位点),前2个位于S区的"a"决定簇之外,后1个则在与X编码框重叠的区域;婴儿-母亲(15对):有9例婴儿与母亲体内的HBV存在不同的突变位点(共25个位点),但仅1例是母亲、新生儿和免疫后婴儿均存在不同的突变位点。结论:(1)新生儿及免疫后婴儿体内的HBV均源自于母亲;(2)HBV的S基因在联合免疫前和免疫后均可发生突变,主要发生在联合免疫前,是否与免疫失败有关尚需进一步研究。

AIM： To explore the characteristics of hepatitis B virus S gene mutation in the vertical transmission after active and passive vaccination. METHODS： Fifteen cases of immunoprophylaxis failure were enrolled in the study.HBV S gene（ including pres-S and S） from the mothers,newborns before active and passive vaccination and 7-month-old infants with immunoprophylaxis failure were detected by PCR amplification. The characteristics of HBV S gene mutation were compared among the 3 groups. RESULTS： The genotype of HBV in the newborns and the infants was the same as that in the mothers. The frequencies of mutation in the 2 fragments of the HBV S gene had no significant difference between the 3 groups. The homology tree model based on HBV S gene was analyzed in the 3 groups,in which every group had their own cluster. There were 15 different mutation sites between 7 pairs of mothers and newborns. There were 3 different mutation sites between 3 pairs of newborns and infants（ nt273A→A /G,nt512C→C /T and nt1139C→A）,among which the first 2 were located in the S gene region but not in the＂a＂determinant,and the latter was located in the overlap region of S and X genes. There were 25 different mutation sites between 9 pairs of mothers and infants,but only 1 case had a different mutation site between the mother,newborn and infant. CONCLUSION： The HBV species in newborns and infants with immunoprophylaxis failure were transmitted from the mothers. The mutations in the HBV S gene with immunoprophylaxis failure happened before and after active and passive vaccination,mainly before vaccination. The relationship between HBV S gene mutations and immunoprophylaxis failure should be further explored.