摘要
目的探讨高效抗反转录病毒疗法（highly active antiretroviral treatment, HAART）治疗24周AIDS患者外周血程序性死亡因子（programmed death-1, PD-1）和配体（Programmed cell death 1 ligand 1, PD-L1）表达水平的特点变化。方法选取HAART治疗的45例艾滋病感染者（AIDS），按CD4^＋T细胞计数分成1—100cells／μl、101～200cells／μl和201～350cells／μl三组，于抗病毒前和抗病毒24周时采集静脉血，同时选取21名健康体检者作对照。运用流式细胞仪检测外周血中CD4^＋T细胞表面PD-1和PD—L1的表达水平，实时荧光定量PCR仪检测血浆病毒载量，数据处理采用t检验，相关性分析采用Pearson相关。结果AIDS感染者治疗前PD-1／PD—L1的表达频率为（1．16±0．26）％和（0．63±0．140）％，均显著高于健康对照组（t分别为6．31和4．27，P=0．000）。抗病毒治疗24周时PD-1／PD—L1在CD4^＋T细胞中的表达频率分别为（0．76±0．14）％和（0．52±0．06）％，与治疗前相比PD-1表达水平显著下降（t=3．77，P=0．000），PD—L1的表达频率也有所下降，但差异无统计学意义（t=1．78，P=0．056）。CD4^＋T细胞基数为201～350cells／μl患者组其PD-1表达频率在治疗24周后平均下调率明显高于另二组（38．54％伽．25．66％和23．77％），而PD—L1的表达也高于1～100cells／μl和101～200cells／μl二组（18．97％vs15．87％和12．31％）。治疗前与治疗后AIDS感染者CD4^＋T细胞数与PD-1表达百分率呈显著负相关（r=-0．434，-0．317，P=0．009和0．031），与病毒载量呈显著正相关（r分别为0．499和0．319，P为0．0049和0．032）。PD—L1表达频率在治疗前与治疗后与CD4^＋T细胞数呈显著负相关（r=-0．454和-0．314，P=0．002和0．012），与病毒载量在治疗前后呈显著正相关（r=0．513和0．428，P=0．000和0．004）。结论AIDS感染者外周血PD-1／PD—L1的表达水平增加，且与疾病进展密切相关。
Objective To discuss the changes in expression of programmed death - 1 （PD-1） and programmed cell death 1 ligand 1 （ PD-Ll） in AIDS patients receiving highly active antiretroviral treatment （ HAART） for 24 weeks. Methods According to the CD4^＋ T cell counts, 45 AIDS patients receiving HAART were divided into three groups （ 1 - 100 cells/ μl, 101 - 200 cells/μl and 201 - 350 cells/ μl ） , Peripheral blood samples were taken before HAART and at 24 weeks after HAART, PD-lIPD-Ll expressions on CD4^＋ T cells were assessed by flow cytometry, Plasma HIV RNA loads were determined by real-time fluorescent quantitative polymerase chain reaction （ PCR）. The data were analyzed with t test and Pearson correlation analysis. Results The PD-1 and PD-L1 expression levels on CD4^＋ T cells in AIDS patients were （ 1. 16 ± 0.26） % and （ 0.63 ± 0. 140） % respectively before HAART, which were significantly higher those of healthy controls （ t = 6.31 and 4. 27, all P 〈 0.01）. The PD-1 and PD-L1 expressions levels were （0.76 ±0. 14） % and （ 0. 52 ± 0. 06） % 24 wwks later. The PD-l expression level declined significantly compared with that before HAART （ t = 3. 77 , P = 0. 000）. The PD-L1 expression level declined too compared with that before HAART, but no statistically significance was found（ t = 1. 78 ,P = 0. 056）. The PD-1 expression level in patients with CD4^＋ T cell count of 201 - 350 showed a remarkable decline than two other groups （38.54% vs. 25.66% and 23.77%） 24 weeks later, The decline rate of PD-L1 expression levels was greater than those of two groups （ 18. 97% vs. 15.87% and 12. 31 %）. The level of PD-1 expression was significantly negatively correlated with CD4＋ T cell count before HAART and 24 weeks later （r = - 0.434 and - 0.3l7;P 〈 0.01 or 0. 05） , and was significantly positively correlated with viral load before HAART and 24 weeks later（ r = 0.499 and 0. 319, P 〈 0.01 or 0. 05）. The PD-L1 expression level was significantly negatively correlated with the CD4^＋ T cell count before HAART and 24 weeks later （r = - 0.454 and - 0. 314, P = 0. 002 and 0.012）, and was significantly positively correlated with viral load before HAART and 24 weeks later （ r = 0. 513 and 0.428, all P = 0. 000 and O. 004）. Conclusion The expression levels of PD/PD-1 were up-regulated in AIDS patients and associated with HIV disease progress
出处
《疾病监测》
CAS
2014年第1期32-36,共5页
Disease Surveillance
基金
浙江省绍兴市重点科技计划项目(No.2011A23016)~~
