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Title: [Role of TLR 9 expression in maternal peripheral blood and placenta in intrauterine transmission of HBV].
Author: Shao YZ, Yan M, Hu N, Wang HR, Fu T, Gao J, Zhang L.
Journal: Zhonghua Liu Xing Bing Xue Za Zhi; 2019 Sep 10; 40(9):1065-1070. PubMed ID: 31594147.
Abstract:
Objective: To explore the role of TLR 9 in intrauterine transmission of hepatitis B virus (HBV) through blood pathway and placenta. Methods: Epidemiological investigation was carried out in 290 HBsAg positive parturients and 45 normal parturients (control group) in Northwest Women and Children Hospital of Shaanxi Province. Enzyme-linked immunosorbent assay (ELISA) was used to detect five serological makers of hepatitis B and TLR 9 levels in peripheral blood of pregnant women and newborns. HBV DNA was detected by real-time fluorescence quantitative PCR. Detection of TLR 9 expression in placenta by immunohistochemical method. A case-control study was conducted to analyze the difference of TLR 9 levels in placenta and peripheral blood of HBsAg- positive pregnant women with intrauterine transmission of HBV. Results: The incidence of dominant HBV infection (DBI), occult HBV infection (OBI) and intrauterine transmission of HBV were 9.28% (27/291), 40.21% (117/291) and 49.48% (144/291) respectively. (1) The level of TLR 9 in peripheral blood of HBsAg-positive parturients, non-HBV intrauterine transmission (NBIT) group and OBI group were significantly lower than that of control group (P<0.001). The level of TLR 9 in DBI group was significantly higher than those in NBIT group and OBI group (P=0.000). (2) The TLR 9 level in HBeAg-negative group was significantly lower than that in HBeAg-positive parturients in OBI group (P=0.01). (3) With the increased severity of intrauterine transmission of HBV in each HBV DNA load group, the TLR 9 level in maternal peripheral blood increased significantly (P<0.05). (4) With the increased severity of intrauterine transmission of HBV, the levels of TLR 9 increased significantly in antiviral therapy, immunoglobulin injection and non-hepatitis B vaccine groups (P<0.05). (5) The expression of TLR 9 in placenta tissues with DBI group was significantly higher than that in OBI group and NBIT group (P<0.05). Conclusions: HBV can inhibit the secretion of TLR 9 in parturient to some extent, but HBeAg can stimulate the secretion of TLR 9. However, with the increased severity of intrauterine transmission of HBV, the level of TLR 9 in parturients is increased by intra-group cross-differentiation. Therefore, TLR 9 is not an independent marker for screening and grouping, but it can be used as an reference indicator for the monitoring and management of HBsAg-positive parturients. 目的： 探讨Toll样受体9（TLR 9）经血液和胎盘途径在HBV宫内传播（BIT）中的作用。 方法： 对陕西省西北妇女儿童医院分娩的290例HBsAg阳性产妇为病例组和45例健康产妇为对照组进行流行病学调查，ELISA法检测产妇及子代外周血乙型肝炎（乙肝）五项和TLR 9水平，实时荧光定量PCR检测HBV DNA水平；免疫组织化学法检测TLR 9在胎盘组织中的表达。采用病例对照研究方法分析发生BIT的HBsAg阳性产妇TLR 9水平差异。 结果： HBsAg阳性产妇所生新生儿发生HBV宫内显性感染（DBI）率、宫内隐匿性感染（OBI）率和BIT率分别为9.28%（27/291）、40.21%（117/291）和49.48%（144/291）。HBsAg阳性产妇及未传播组（NBIT）和OBI组的TLR 9水平均显著低于对照组（P<0.001），DBI组的TLR 9水平显著高于NBIT组和OBI组（P=0.000）；OBI组中HBeAg阴性组的TLR 9水平显著低于HBeAg阳性组（P=0.01）；HBV DNA载量分层中均随着BIT程度的加重，产妇外周血TLR 9含量明显增加（P<0.05）；抗病毒治疗、注射免疫球蛋白和未接种乙肝疫苗组，均随着BIT程度的加重，产妇外周血TLR 9含量明显增加（P<0.05）；DBI的胎盘组织中TLR 9表达显著高于OBI组和NBIT组（P<0.05）。 结论： HBV一定程度下会抑制产妇体内分泌TLR 9，但HBeAg能刺激母体TLR 9分泌，随着BIT程度的加重，其体内TLR 9水平呈增高的组内交叉分化现象，因此，TLR 9不是一个能独立筛选分组的标记，但可以做为HBsAg阳性产妇监测管理的参考指标。.

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