新生儿乙肝疫苗接种阻断HBV母婴传播与HLA-DR区域基因相关性的研究

Association between prevention of hepatitis B virus maternal-infantile transmission by hepatitis B vaccine inoculation and HLA-DR gene domain

目的:研究HBV母婴传播导致新生儿接种乙肝疫苗免疫失败与HLA-DR区域基因的相关性,以及HLA-DR基因控制机体对乙肝疫苗免疫应答的机理。方法:60例HBsAg阳性产妇所分娩的新生儿,均于出生后24h内、1月、6月龄共接种3次乙肝疫苗,每次30μg,随访至幼儿3周岁时采其外周静脉血检测乙肝血清标志物,根据检测结果分为两组:①免疫失败组:HBsAg阳性和/或抗-HBs阴性,共12例;②免疫成功组:HBsAg阴性,抗-HBs阳性,共48例。采用聚合酶链反应-序列特异性引物法(PCR-SSP)检测其HLA-DR3、HLA-DR4、HLA-DR13、HLA-DR15基因分布及频率。结果:①两组观察对象性别、母亲HBeAg阳性率、宫内感染率及出生体重差异均无统计学意义(P>0.05),具有可比性。②免疫失败组幼儿HLA-DR3基因频率明显高于免疫成功组,HBV母婴传播导致新生儿免疫失败与HLA-DR3呈强关联(OR=7.86,P<0.05),与HLA-DR15亦呈关联性(OR=0.14,P<0.05),HLA-DR4、HLA-DR13基因频率在两组研究对象中差异均无统计学意义(P>0.05)。结论:HBV母婴传播导致新生儿接种乙肝疫苗免疫失败与HLA-DR抗原有关,HLA-DR3可能为免疫失败的易感基因,HLA-DR15则可能为其保护基因。

Objective:To study the relationship between hepatitis B vaccine(HBVac)failure in-duced by maternal-infantile transmission and HLA-DR,and immunoregulatory mechanisms of HLA-DR which control the responsiveness to HBVac.Methods:Sixty cases of neonates of HBsAg-positive mothers were injected with HBVac(30μg per time)within24hours,1month,6months after birth respectively.The HBV markers were tested when the children were3years old.Then the children were divided into two groups:those with positive HBsAg or negative anti-HBs were included in post-prophylaxis failure group(12cases),while those with positive anti-HBs in post-prophylaxis success group(48cases).By using PCR-SSP methods,the HLA-DR3,HLA-DR4,HLA-DR13,and HLA-DR15were tested respectively.Results:①There were no significant differences of sex,HBeAg-positive rates of mothers,rates of intrauterine infection and birth weights of neonates between the two groups (P>0.05).②The gene frequency of HLA-DR3in neonates of post-prophylaxis failure group was significantly higher than that in post-prophylaxis success group(P<0.05).The post-prophylaxis failure of neonates to HBV carrier mothers was positively correlated with HLA-DR3(P<0.05),but correlated negatively with HLA-DR15(P<0.05).There was no significant difference of the frequencies of HLA-DR4and HlA-DR13between the two groups(P>0.05).Conclu sion:The hepatitis B vaccine failure in infants of HBV carrier mothers is associated with human leukocyte antigen-DR.HLA-DR3may be the susceptible gene of post-prophylaxis failure neonates,but HLA-DR15probably is the pro-tective gene.