HBV感染的孕妇外周血microRNA表达谱及免疫因子表达的差异

Expression profiles of microRNA in peripheral blood mononuclear cells and immune factors in pregnant women with hepatitis B virus infection

目的探讨乙肝病毒(hepatitis B virus,HBV)感染孕妇外周血单核细胞(peripheral blood mononuclear cell,PBMC)中微小RNA(microRNA,miRNA)表达谱的变化和外周血免疫因子的表达差异。方法应用高通量测序对182例HBV感染孕妇、40名无HBV感染孕妇和35名无HBV感染非妊娠期妇女的PBMC中的RNA进行检测,用间接酶联免疫吸附测定法检测外周血中细胞因子的变化。结果与无HBV感染的孕妇比较,HBV感染孕妇的PBMC有18个差异表达的miRNA(P<0.01),其中miR-3607-3p、miR-20a、miR-1296、miR-153-1和miR-X4能直接诱导调控靶基因IL-10、IL-18、IL-16、单核细胞趋化蛋白-1(MCP-1)、核孔蛋白50(NUP50)和趋化因子受体1(CCR1)的转录水平。另外,HBV感染孕妇外周血细胞因子IL-10、IL-18、IL-16和MCP-1明显上调(P<0.01),且IL-16和MCP-1的表达水平与HBV病毒载量呈高度相关关系。结论HBV感染孕妇的miRNA表达谱及细胞因子发生明显变化,提示miRNA和细胞因子可能均参与HBV感染孕妇的免疫反应。

Objective To determine the expression profile of microRNA (miRNA) in peripheral blood mononuclear cells (PBMC) and immune factors in pregnant women with hepatitis B virus (HBV) infection. Methods A total of 182 pregnant women infected with HBV were randomly selected, with 40 healthy pregnant women and 35 non-pregnant women as controls. High-throughput sequencing was used to detect RNA in the PBMC of all subjects. Indirect ELISA method was used to determine the changes of cytokines in peripheral blood samples. Results Compared with the control group, 18 differentially expressed miRNA were identified in those with HBV infection (P < 0.01). Among these, miR-3607-3p, miR-20a, miR-1296, miR-153-1 and miR-X4 may directly regulate the transcriptional level of target genes including IL-10, IL-18, IL-16, MCP-1, NUP50 and CCR1. Meanwhile, peripheral blood cytokines IL-10, IL-18, IL-16 and MCP-1 were significantly increased in those with HBV infection (P<0.01), with the expression level of IL-16 and MCP-1 being strongly correlated with the viral load. Conclusion The expression profiles of miRNA in PBMC and cytokines in peripheral blood can change significantly during pregnancy, both may be involved in the immune response to HBV infection.