HBsAg阳性母亲HBeAg和新生儿调节性T淋巴细胞关系及对HBV宫内传播的影响

Relationship between HBeAg from HBsAg positive mothers and regulatory T cells in neonates and its influence on HBV intrauterine transmission

目的探讨HBsAg阳性母亲的HBeAg与新生儿CD4＋CD25＋Foxp3＋调节性T淋巴细胞（Treg）含量的关系以及对增加新生）LHBV宫内传播发生风险的影响。方法选择太原市第三人民医院妇产科分娩的270对HBsAg阳性母亲及其新生儿，收集一般人口学特征及分娩情况等资料，采用荧光定量聚合酶链式反应（FQ．PCR）和化学发光免疫试验（CLIA）检测母婴外周血HBVDNA及HBV血清学标志物；流式细胞术（FCM）检测新生儿外周血Treg等免疫细胞含量。结果母亲HBeAg阳性是HBV宫内传播的危险因素（OR=4．08。95％CI：1．89～8．82）；母亲HBeAg阳性者新生儿Treg含量高于阴性者（Z=2．29，P=0．022）；按母亲HBeAg滴度分为5组，各组问新生儿Treg、HBeAg及母亲HBVDNA随母亲HBeAg滴度增高呈上升趋势，差异均有统计学意义（X2=18．73，P〈0．001；X2=181．60，P〈0．001；X2=183．09，P〈0．001）。偏相关分析中控制母亲HBVDNA以及新生儿HBeAg后，母亲HBeAg与新生儿Treg呈正相关（rs=0．19，P=0．039）。新生儿Treg与浆细胞样树突状细胞（pDC）、CD4＋T淋巴细胞含量为负相关（rs=-0．21，P=0．017；n=-0．23，P=0．009）。结论HBsAg阳性母亲的HBeAg可能通过上调新生儿Treg含量，影响树突状细胞和效应T淋巴细胞的功能及其对HBV的免疫应答，从而增加新生儿发生HBV宫内传播的风险。

Objective To explore the relationship between HBeAg in HBsAg positive mothers and CD4 ＋ CD25＋ Foxp3 ＋ regulatory T cells （Treg） in newborns, as well as how they would influence the increasing risk on HBV intrauterine transmission. Methods We collected information on general demographic characteristics and delivery on 270 HBsAg positive mothers and their newborns from the Third People＇ s Hospital of Taiyuan. Fluorescence quantitative polymerase chain reaction （FQ-PCR） and chemiluminescence immunoassay （CLIA） were used to detect HBV DNA and HBV serological markers in peripheral blood from both mothers and neonates, The expression of Treg and other immune cells in peripheral blood of neonates were detected with flow cytometry （FCM）. Results Maternal HBeAg positive rates were associated with an increased risk of intrauterine transmission （OR=4.08, 95% CI： 1.89-8.82）. Rates of Yreg in newborns born to HBsAg-positive mothers were higher than that of the negative group （Z----2.29, P=0.022）. Each pair of the subjects was assigned to five different groups according to the HBeAg titers of mothers. Frequencies of both Treg and HBeAg in newborns and HBV DNA in mothers between the above said 5 groups showed similar trends of changing patterns and the differences between groups were statistically significant （X2= 18.73, P〈0.001; X2= 181.60, P〈0.001; X2= 183.09, P〈0.001）. Results from partial correlation analysis showed that after adjusting for neonatal HBeAg and maternal HBV DNA, mother＇ s HBeAg titers were positively related to the percentage of Treg in their newborns （r,=0.19, P=0.039）. In addition, the frequencies of Treg were negatively correlated with pDC and CD4 ＋ T cell in their newborns （r,=-0.21, P=0.017; r,=-0.23, P=0.009）. Conclusion HBeAg from HBsAg positive mothers might have inhibited the function of neonatal DC cells and T cells to reduce the immune response to HBV by up-regulating the proportion of Treg and finally increased the risk of HBV intrauterine transmission.