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目的探讨人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染患者接受抗反转病毒治疗(antiretroviral therapy,ART)前CD4~+及CD8~+T淋巴细胞表达水平在免疫重建效果预测中的价值。方法 HIV感染患者48例,分别于ART治疗前及治疗6个月后采用实时荧光定量PCR技术检测HIV-RNA,观察HIV-RNA转阴情况;采用流式细胞技术检测CD4~+T淋巴细胞、CD8~+T淋巴细胞,观察CD4~+T淋巴细胞上升情况;比较治疗6个月后HIV-RNA转阴与未转阴组,CD4~+T淋巴细胞上升与未上升组治疗前Th1、Th2、Th17、调节性T(regulatory,Treg)细胞、CD4~+T淋巴细胞、CD8~+T淋巴细胞百分比及Th1/Treg、Th2/Treg、Th17/Treg、Th1/Th17、Th2/Th17、Th1/Th2、CD4~+/CD8~+淋巴细胞比值等指标;绘制ROC曲线,分析治疗前CD4~+T淋巴细胞组成预测ART治疗6个月后HIV-RNA阴转、CD4~+T淋巴细胞上升的效能。结果 ART治疗6个月后失访22例,余26例中HIV-RNA转阴22例、未转阴4例,CD4~+T淋巴细胞上升22例、未上升4例;HIV-RNA转阴组治疗前Th17细胞百分比[(6.89±5.23)%]、CD4~+/CD8~+(0.44±0.29)高于HIV-RNA未转阴组[(1.47±1.26)%、0.14±0.09],Th2/Th17(1.80±1.32)低于HIV-RNA未转阴组(4.22±0.63)(P<0.05);CD4~+T淋巴淋巴细胞上升组治疗前Th17细胞百分比[(6.62±5.24)%]、CD4~+/CD8~+(0.47±0.29)高于CD4~+T淋巴细胞未上升组[(2.05±1.68)%、0.13±0.08],Th2/Th17(1.66±0.88)低于CD4~+T淋巴细胞未上升组(4.81±1.27)(P<0.05);治疗前Th17细胞百分比、Th2/Th17、CD4~+/CD8~+预测治疗后6个月HIV-RNA转阴的AUC分别为0.850(95%CI:0.688~1.000,P<0.001)、0.933(95%CI:0.827~1.000,P<0.001)、0.817(95%CI:0.614~1.000,P<0.001),最佳截断值分别为3.06%、2.45、0.628,灵敏度分别为97.0%、66.7%、98.0%,特异度分别为72.3%、90.9%、71.4%;预测治疗后6个月CD4~+T淋巴细胞上升的AUC分别为0.768(95%CI:0.567~0.969,P<0.001)、0.976(95%CI:0.918~1.000,P<0.001)、0.875(95%CI:0.730~1.000,P<0.001),最佳截断值分别为3.35%、2.45、0.268,灵敏度分别为56.2%、91.3%、77.3%,特异度分别为96.8%、96.2%、97.1%。结论 Th17细胞百分比、Th2/Th17、CD4~+/CD8~+在预测ART治疗短期内免疫重建效果中有一定价值。
Objective To investigate the expression of CD4 ~ + and CD8 ~ + T lymphocytes in patients with human immunodeficiency virus (HIV) infection before immunotherapy with antiretroviral therapy (ART). Methods HIV-RNA was detected in 48 patients with HIV infection before and 6 months after treatment. The HIV-RNA negative was detected by real-time fluorescence quantitative PCR. CD4 ~ + T lymphocytes were detected by flow cytometry, CD8 ~ + T lymphocytes, CD4 ~ + T lymphocytes increased; compared 6 months after treatment of HIV-RNA negative and non-negative group, CD4 ~ + T lymphocytes increased and did not increase before treatment Th1, Th2 , Th17, regulatory Treg cells, CD4 ~ + T lymphocytes, CD8 ~ + T lymphocytes and Th1 / Treg, Th2 / Treg, Th17 / Treg, Th1 / Th17, Th2 / Th17, Th1 / Th2, CD4 ~ + / CD8 ~ + lymphocyte ratio and other indicators; ROC curve was drawn to analyze the composition of CD4 ~ + T lymphocytes before treatment predicted HIV-RNA overcast 6 months after ART treatment, CD4 ~ + T lymphocytes increased efficacy. Results Twenty-two patients were lost to ART after 6 months of treatment. Among the remaining 26 cases, 22 cases were negative for HIV-RNA, 4 cases were not negative, CD4 + T-lymphocyte increased in 22 cases and did not increase in 4 cases. HIV- The percentage of Th17 cells in the group before treatment [(6.89 ± 5.23)%] and CD4 ~ + / CD8 + (0.44 ± 0.29) were significantly higher than those in the group without HIV-RNA [1.47 ± 1.26%, 0.14 ± 0.09] /Th17(1.80 ± 1.32) was lower than that in HIV-RNA non-negative group (4.22 ± 0.63) (P <0.05); The percentage of Th17 cells in CD4 ~ + T lymphocyte ascending group before treatment was (6.62 ± 5.24)%, The levels of CD4 ~ + / CD8 ~ + (0.47 ± 0.29) in CD4 ~ + T lymphocytes were significantly higher than those in CD4 ~ + T lymphocytes [(2.05 ± 1.68)%, 0.13 ± 0.08] The percentage of Th17 cells before treatment, Th2 / Th17, CD4 ~ + / CD8 + predicted the HIV-RNA negative AUC of 6 months after treatment was 0.850 (P <0.05) (95% CI: 0.827-1.000, P <0.001), 0.817 (95% CI: 0.614-1.000, P <0.001), and the best cutoffs were 3.06 %, 2.45,0.628, the sensitivity was 97.0%, 66.7%, 98.0%, specificity were 72.3%, 90.9%, 71.4% respectively; The predicted AUC of CD4 ~ + T lymphocytes in 6 months after treatment were 0.768 95% CI: 0.567 ~ 0.969, P <0.0 (95% CI: 0.918-1.000, P <0.001) and 0.875 (95% CI: 0.730-1.000, P <0.001). The best cut-off values were 3.35%, 2.45 and 0.268, respectively, and the sensitivities were 56.2 %, 91.3% and 77.3%, respectively. The specificities were 96.8%, 96.2% and 97.1% respectively. Conclusion The percentages of Th17 cells, Th2 / Th17 and CD4 ~ + / CD8 ~ + have some value in predicting the effect of immune reconstruction in short-term ART.