CD4^+及CD8^+T淋巴细胞预测人类免疫缺陷病毒感染患者抗反转录病毒治疗效果的价值

Value of CD4^+ and CD8^+ T lymphocytes to predicting the therapeutic effect of antiretroviral therapy on HIV infection

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 explore the value of the CD4^+ and CD8^+T lymphocyte to predicting the therapeutic effect on immune reconstitution before antiretroviral therapy(ART)in patients with human immunodeficiency virus(HIV)infection.Methods Forty-eight patients with HIV infection received HIV-RNA before and after 6-month ART to observe the negative conversion rate.CD4^+and CD8^+T lymphocytes were detected by flow cytometry to observe the increase of CD4^+T lymphocyte.The percentages of helper T(Th)1,Th2,Th17,regulatory T(Treg)cells,CD4^+T lymphocytes and CD8^+T lymphocytes,as well as Th1/Treg,Th2/Treg,Th17/Treg,Th1/Th17,Th2/Th17,Th1/Th2 and CD4^+/CD8^+T lymphocytes before ART were compared between HIV-RNA negative conversion patients(negative group)and HIV-RNA non-negative conversion patients(non-negative group),and between increased CD4^+T lymphocytes patients(increased group)and non-increased CD4^+T lymphocytes patients(non-increased group).ROC was used to analyze the predictive efficiency of CD4^+T lymphocyte composition before ART on predicting HIV-RNA negative conversion and increased CD4^+T lymphocytes after 6-month ART.Results After 6-month ART,22 patients were lost,and in the other 26 patients,HIV-RNA conversed negative in 22 patients and not conversed negative in 4patients,and CD4^+T lymphocytes increased in 22 patients and not increased in 4patients.The percentage of Th17cells((6.89±5.23)%)and CD4^+/CD8^+(0.44±0.29)were significantly higher in negative group than those in non-negative group((1.47±1.26)%,0.14±0.09),and Th2/Th17 was significantly lower in negative group(1.80±1.32)than that in non-negative group(4.22±0.63)(P<0.05).The percentage of Th17cells((6.62±5.24)%)and CD4^+/CD8^+(0.47±0.29)before ART were significantly higher in increased group than those in non-increased group((2.05±1.68)%,(0.13±0.08)),and Th2/Th17 was significantly lower in increased group(1.66±0.88)than that in non-increased group(4.81±1.27)(P<0.05).The AUC values of the percentage of Th17 cells,Th2/Th17 and CD4^+/CD8^+T lymphocytes before ART for predicting HIV-NRA negative conversion rate after 6-months ART were0.850(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),the optimal cut-off values were 3.06%,2.45 and 0.628,the sensitivities were 97.0%,66.7% and 98.0%,and the specificities were 72.3%,90.9% and 71.4% respectively.The AUCvalues for predicting increased CD4^+T lymphocytes were 0.768(95%CI:0.567-0.969,P<0.001),0.976(95%CI:0.918-1.000,P<0.001)and 0.875(95%CI:0.730-1.000,P<0.001),the optimal cut-off values were 3.35%,2.45 and 0.628,the sensitivities were56.2%,91.3% and 77.3%,and the specificities were 96.8%,96.2% and 97.1%,respectively.Conclusion The percentage of Th17,Th2/Th17 and CD4^+/CD8^+T lymphocytes have certain predictive values to predicting immune reconstitution in a short time of ART.