【摘要】 目的探讨孕中晚期乙型肝炎病毒(hepatitis B virus,HBV)感染孕妇外周血T细胞亚群的变化及临床意义。方法选取2017年11月至2019年5月于哈尔滨医科大学附属第四医院就诊的150例孕中晚期(孕周≥24周)HBV感染孕妇为研究对象,其中慢性HBV携带孕妇135例,慢性乙型肝炎(chronic hepatitisB,CHB)孕妇15例,另选取20例同期健康体检的孕中晚期孕妇为健康对照组。采用流式细胞术检测所有研究对象外周血中T细胞亚群百分比,比较慢性HBV感染组、CHB组及健康对照组孕妇外周血中T细胞亚群百分比的差异。根据HBV DNA载量,将慢性HBV感染组孕妇分为中高病毒载量组(HBV DNA≥10~4 IU/ml)和低病毒载量组(HBV DNA <1.0×10~4 IU/ml),比较中高病毒载量组、低病毒载量组和健康对照组间T细胞亚群百分比的差异。根据乙型肝炎病毒e抗原(hepatitis B virus e antigen,HBeAg)状态,将慢性HBV感染组孕妇分为HBeAg阳性组和HBeAg阴性组,比较两组间T细胞亚群百分比的差异。结果 CHB组、慢性HBV感染组及健康对照组孕妇外周血CD4~+T细胞百分比[(30.4±3.9)%vs(36.5±5.1)%vs(39.5±4.2)%]、CD8~+T细胞百分比[(38.9±4.3)%vs(35.7±5.8)%vs(32.9±3.7)%]及CD4~+/CD8~+比值(0.7±0.1 vs 1.0±0.2 vs 1.2±0.1)差异均有统计学意义(F值分别为14.579、5.115、14.029,P均<0.05),CD3~+T细胞百分比[(70.8±6.0)%vs(73.3±6.0)%vs(72.5±6.4)%]差异无统计学意义(F=1.178,P=0.310)。与健康对照组相比,CHB组及慢性HBV感染组CD4~+T细胞百分比及CD4~+/CD8~+比值显著降低,CD8~+T细胞百分比显著升高(P均<0.05)。与慢性HBV感染组相比,CHB组CD4~+T细胞百分比及CD4~+/CD8~+比值显著降低,CD8~+T细胞百分比显著升高(P均<0.05)。中高病毒载量组、低病毒载量组和健康对照组孕妇CD4~+T细胞百分比[(35.3±4.9)%vs(38.2±4.9)%vs(39.5±4.2)%]、CD8~+T细胞百分比[(36.3±5.9)%vs(34.5±5.3)%vs(32.9±3.7)%]及CD4~+/CD8~+比值(0.9±0.2 vs 1.1±0.2 vs 1.2±0.1)差异有统计学意义(F值分别为8.898、4.555、9.347,P均<0.05),CD3~+T细胞百分比[(73.3±6.2)%vs(73.3±5.9)%vs(72.5±6.4)%)]差异无统计学意义(F=0.148,P=0.863)。与低病毒载量组及对照组相比,中高病毒载量组CD4~+T细胞百分比和CD4~+/CD8~+比值显著降低,CD8~+T细胞百分比显著升高(P均<0.05)。与HBe Ag阴性组相比,HBe Ag阳性组孕妇CD4~+T细胞百分比[(35.4±5.0)%vs(38.0±4.9)%]和CD4~+/CD8~+比值(0.9±0.2 vs 1.1±0.2)显著降低(t=-2.981、-3.119,P=0.003、0.002),CD8~+T细胞[(36.7±5.9)%vs(34.5±5.4)%]百分比显著升高(t=2.192,P=0.030),CD3~+T细胞百分比[(73.4±5.9)%vs(73.1±6.2)%]差异无统计学意义(t=0.262,P=0.794)。结论妊娠合并HBV感染相较于健康孕妇外周血中T细胞亚群发生变化,HBV复制、免疫激活可加重细胞免疫功能的紊乱。检测T细胞亚群在临床上可间接了解HBV感染孕妇的免疫状态,使HBV的作用机制得到进一步明确。更多还原

【Abstract】 Objective To investigate the changes and clinical significances of T cell subset in pregnant women infected with hepatitis B virus(HBV) in middle and late pregnancy. Methods Total of 150 pregnant women infected with HBV in middle and late pregnancy in the Fourth Affiliated Hospital of Harbin Medical University from November 2017 to May 2019 were selected, including 15 cases with chronic hepatitis B(CHB) and 135 cases with chronic HBV infection. Another 20 pregnant women in middle and late pregnancy were selected as healthy controls. Flow cytometry was used to detect the percentage of T cell subsets in the peripheral blood of all subjects, and the difference of T cell subsets in the peripheral blood of pregnant women in chronic HBV infection group, CHB group and healthy control group were compared. According to HBV DNA load, pregnant women in chronic HBV infection group were divided into medium and high viral load group(HBV DNA ≥ 10~4 IU/ml) and low viral load group(HBV DNA < 1.0 × 10~4 IU/ml), and the difference of T cell subpopulation percentage was compared. According to the state of hepatitis B virus e antigen(HBeAg), pregnant women in chronic HBV infection group were divided into HBeAg positive group and HBeAg negative group, and the difference of T cell subpopulation percentage between the two groups was compared. Results The differences of CD4~+T cells percentage [(30.4 ± 3.9)% vs(36.5 ± 5.1)% vs(39.5 ± 4.2)%], CD8~+T cells percentage [(38.9 ± 4.3)% vs(35.7 ± 5.8)% vs(32.9 ± 3.7)%] and CD4~+/CD8~+ ratio(0.7 ± 0.1 vs 1.0 ± 0.2 vs 1.2 ± 0.1) of pregnant women in CHB group, chronic HBV infection group and healthy control group were statistically significant(F = 14.579, 5.115, 14.029; all P < 0.05), and the difference of CD3~+T cells percentages [(70.8 ± 6.0)% vs(73.3 ± 6.0)% vs(72.5 ± 6.4)%] were not statistically significant(F = 1.178, P = 0.310). Compared with those in healthy control group, the percentage of CD4~+T cells and the ratio of CD4~+/CD8~+ of patients in CHB group and chronic HBV infected group decreased significantly, while the percentage of CD8~+T cells increased significantly(all P < 0.05). Compared with those in chronic HBV infection group, the percentage of CD4~+T cells and the ratio of CD4~+/CD8~+ of patients in CHB group reduced significantly, and the percentage of CD8~+T cells increased significantly(all P < 0.05). The differences of CD4~+T cells percentage [(35.3 ± 4.9)% vs(38.2 ± 4.9)% vs(39.5 ± 4.2)%], CD8~+T cells percentage [(36.3 ± 5.9)% vs(34.5 ± 5.3)% vs(32.9 ± 3.7)%] and CD4~+/CD8~+ ratio(0.9 ± 0.2 vs 1.1 ± 0.2 vs 1.2 ± 0.1) of patients in medium and high viral load group, low viral load group and healthy control group were statistically significant(F = 8.898, 4.555, 9.347; P < 0.05), and the difference of CD3~+T cells percentage was not statistically significant(F = 0.148, P = 0.863). Compared with medium and high viral load group and healthy control group, the percentage of CD4~+T cells and CD4~+/CD8~+ ratio decreased significantly, the percentage of CD8~+T cells increased significantly(all P < 0.05). Compared with patients in HBeAg negative group, the percentage of CD4~+T [(35.4 ± 5.0)% vs(38.0 ± 4.9)%] cells and CD4~+/CD8~+(0.9 ± 0.2 vs 1.1 ± 0.2) ratio of patients in HBeAg positive group decreased significantly(t =-2.981,-3.119; P = 0.003, 0.002), and the percentage of CD8~+T cells [(36.7 ± 5.9)% vs(34.5 ± 5.4)%] increased significantly(t = 2.192, P = 0.030). There was no statistically significant difference of CD3~+T cells percentage of patients between HBeAg positive group and HBeAg negative group [(73.4 ± 5.9)% vs(73.1 ± 6.2)%; t = 0.262, P = 0.794]. Conclusions Compared with healthy pregnant women, the T cell subsets in peripheral blood changed in pregnant women with HBV infection. HBV replication and immune activation can aggravate the disorder of cellular immune function. Detection of T cell subset can indirectly understand the immune function status of pregnant women with HBV infection, and furtherlly clarify the mechanisms of HBV action.更多还原