T淋巴细胞亚群及多个细胞因子的变化与儿童乙型肝炎病毒相关性肾炎相关性分析

Correlation analysis of T lymphocyte subsets and cytokines with hepatitis B virus-associated-glomerulonephritis in children

目的:探讨儿童乙型肝炎病毒(HBV)相关性肾炎(HBV-GN)中T淋巴细胞亚群及多个细胞因子的变化及其与HBV-DNA的相关性。方法:收集2012年9月至2016年9月在甘肃省人民医院儿科和兰州大学附属第一医院感染科明确诊断为HBV-GN的41例初治患儿为研究对象(HBV-GN组),收集同期就诊的HBV携带患儿(慢性HBV感染,肝肾功能正常,24 h尿蛋白定量正常;无镜下血尿,近期无感冒、发热等症状)40例为对照组。比较HBV-GN组与对照组患儿T淋巴细胞亚群、肿瘤坏死因子-α(TNF-α)、γ干扰素(IFN-γ)、白细胞介素(IL)-2、IL-4、IL-6、IL-8、IL-10细胞因子水平的变化,分析HBV-DNA与各细胞因子间的相关性。结果:HBV-GN组CD3+T淋巴细胞比例、CD4+T淋巴细胞比例及CD4+/CD8+值较对照组降低(分别为0.632±0.052比0.692±0.047、0.204±0.050比0.466±0.038、0.006±0.002比0.017±0.003,t=1.025、3.342、5.234,均P<0.05),CD8+T淋巴细胞比例增高(0.411±0.023比0.220±0.043,t=4.452,P<0.01),差异均有统计学意义。HBV-GN组中血清IL-2、IFN-γ均低于对照组[(23.36±2.55)ng/L比(36.33±1.24)ng/L,(19.20±2.18)ng/L比(61.25±2.08)ng/L,均P<0.05],而TNF-α、IL-4、IL-6、IL-8、IL-10水平均高于对照组[分别为(19.60±1.46)ng/L比(6.68±2.32)ng/L、(13.65±3.34)ng/L比(1.35±1.52)ng/L、(5.57±1.02)ng/L比(1.43±0.57)ng/L、(26.32±3.45)ng/L比(9.68±2.55)ng/L、(19.82±2.78)ng/L比(1.02±0.56)ng/L,均P<0.01]。HBV-GN患儿血清中HBV-DNA水平与IFN-γ、IL-2呈负相关(r=-0.985、-0.943,均P<0.05),与TNF-α、IL-4、IL-6、IL-8、IL-10水平呈正相关(r=0.942、0.966、0.953、0.944、0.963,均P<0.05)。结论:在HBV-GN的发病过程中存在CD4+/CD8+T淋巴细胞比例的失衡及各细胞因子水平的异常,在HBV-GN的治疗中应进行HBV-DNA及细胞因子联合监测,以动态评估病情变化及治疗效果。

Objective To investigate the changes of T lymphocyte subsets and cytokines in children with he-patitis B virus(HBV)-associated glomerulonephritis(HBV-GN),and their relationship with HBV-DNA load.Methods Forty-one children who was the first diagnosed with HBV-GN in Department of Pediatrics,the People′s Hospital of Gansu Province and Institute of Infectious Diseases,the First Hospital of Lanzhou University from September 2012 to September 2016 were collected as the objects(HBV-GN group).At the same time,the 40 patients with HBV infection(chronic HBV infection,normal liver and kidney function,normal 24-hour proteinuria quantitation,no hematuria under the microscope,no recent symptoms of cold and fever,etc.)were enrolled as the control group.The levels of T lymphocyte subset,tumor necrosis factorα(TNF-α),interferon-γ(IFN-γ),interleukin(IL)-2,IL-4,IL-6,IL-8 and IL-10 in the HBV-GN group and the control group were compared,and the relationship between HBV-DNA and cell factors was farther analyzed.Results Compared with the control group,the proportions of CD3+T,CD4+T lymphocyte and CD4+/CD8+ratio decreased in the HBV-GN group(0.632±0.052 vs.0.692±0.047,0.204±0.050 vs.0.466±0.038,0.006±0.002 vs.0.017±0.003,t=1.025,3.342,5.234,all P<0.05),and the proportions of CD8+T lymphocyte was significantly higher than that in the control group(0.411±0.023 vs.0.220±0.043,t=4.452,P<0.01).Besides,IL-2 and IFN-γlevels in the HBV-GN group were significantly lower than those in the control group[(23.36±2.55)ng/L vs.(36.33±1.24)ng/L,(19.20±2.18)ng/L vs.(61.25±2.08)ng/L,all P<0.05],and the serum levels of TNF-α,IL-4,IL-6,IL-8,and IL-10 were significantly higher than those in the control group[(19.60±1.46)ng/L vs.(6.68±2.32)ng/L,(13.65±3.34)ng/L vs.(1.35±1.52)ng/L,(5.57±1.02)ng/L vs.(1.43±0.57)ng/L,(26.32±3.45)ng/L vs.(9.68±2.55)ng/L,(19.82±2.78)ng/L vs.(1.02±0.56)ng/L,all P<0.01].Moreover,in HBV-GN patients,there was negative correlation between HBV-DNA load and IFN-γ,IL-2(r=-0.985,-0.943,all P<0.05),and positive relationship in HBV-DNA load with TNF-α,IL-4,IL-6,IL-8 and IL-10 levels(r=0.942,0.966,0.953,0.944,0.963,all P<0.05).Conclusions There is an CD4+/CD8+imbalance and an abnormal level of cell factors in HBV-GN progression.In further HBV-GN treatment,HBV-DNA and the cell factors should be detected simultaneously to dynamically eva-luate the illness change and the clinical curative effect.