系统性红斑狼疮患者程序性死亡因子-1和细胞毒T淋巴细胞相关抗原-4水平

Expression of programmed death-l and T lymphocyte-associated molecule antigen-4 in patients with systemic lupus erythematosus

目的分析程序性死亡因子-1(PD-1)和细胞毒T淋巴细胞相关抗原-4(CTLA-4)在系统性红斑狼疮(SLE)患者中的水平。方法收集2015年6月至2016年3月在我院初诊为SLE的56例患者作为观察组,根据SLE疾病活动指数(SLEDAI)标准将所有患者分为两组,稳定期组(28例)和活动期组(28例)。另选取同期在我院接受体检的28名健康志愿者作为对照组。采用流式细胞仪检测空腹静脉血的CD4+T及CD8+T淋巴细胞上的PD-1及CTLA-4表达。结果与对照组比较,稳定期和活动期SLE的CD4+PD-1+T淋巴细胞(4.46%±0.95%vs.2.93%±0.84%,t=6.38,P<0.001;5.92%±0.86%vs.2.93%±0.84%,t=13.16,P<0.001)和CD8+PD-1+T淋巴细胞(6.57%±0.89%vs.3.31%±0.84%,t=14.10,P<0.001;7.37%±0.97%vs.3.31%±0.84%,t=16.74,P<0.001)明显增高;稳定期和活动期SLE的CD4+CTLA-4+T淋巴细胞(1.03%±0.38%vs.1.34%±0.47%,t=2.68,P=0.01;0.73%±0.36%vs.1.34%±0.47%,t=5.38,P<0.001)及CD8+CTLA-4+T淋巴细胞百分比(0.35%±0.32%vs.0.69%±0.31%,t=4.04,P<0.001;0.13%±0.12%vs.0.69%±0.31%,t=8.91,P<0.001)明显降低。与稳定期SLE比,活动期SLE的CD4+PD-1+T淋巴细胞(t=6.03,P<0.001)及CD8+PD-1+T淋巴细胞百分比(t=3.22,P=0.003)明显增高,CD4+CTLA-4+T淋巴细胞(t=3.03,P=0.01)及CD8+CTLA-4+T淋巴细胞百分比(t=3.41,P=0.002)明显降低。CD4+PD-1+的表达与CD4+CTLA-4+(r=-0.85,P<0.001)、CD8+PD-1+的表达与CD8+CTLA-4+呈负相关性(r=-0.78,P<0.001)。结论 PD-1和CTLA-4参与SLE的发生发展过程,可能通过一定途径抑制PD-1或增高CTLA-4的表达有望成为SLE的新治疗靶点。

Objective To investigate the programmed death-l(PD-1) and cytotoxic T lymphocyteassociated molecule antigen-4(CTLA-4) in patients with systemic lupus erythematosus(SLE). Methods From June 2015 to March 2016, 56 case SLE patients were collected, all the patients were divided into active SLE group(28 cases) and inactive SLE group(28 cases). 28 healthy volunteers were collected as the control group. CD4+PD-1+ T lymphocyte, CD8+PD-1+ T lymphocyte, CD4+CTLA-4+ T lymphocyte and CD8+CTLA-4+ T lymphocyte in peripheral blood were detected by flow cytometry and compared within 3 groups. Results Compared with the control group, the CD4+PD-1+ T lymphocyte(4.46%±0.95% vs. 2.93%±0.84%, t=6.38, P<0.001; 5.92%±0.86% vs. 2.93%±0.84%, t=13.16, P<0.001) and CD8+PD-1+ T lymphocyte percentage(6.57%±0.89% vs. 3.31%±0.84%, t=14.10, P<0.001; 7.37%±0.97% vs. 3.31%±0.84%, t=16.74, P<0.001) had significantly increased and CD4+CTLA-4+ T lymphocyte(1.03%±0.38% vs. 1.34%±0.47%, t=2.68, P=0.01; 0.73%±0.36% vs. 1.34%±0.47%, t=5.38, P<0.001) and CD8+CTLA-4+ T lymphocyte percentage(0.35%±0.32% vs. 0.69%±0.31%, t=4.04, P<0.001; 0.13%±0.12% vs. 0.69%±0.31%, t=8.91, P<0.001) had decreased in 2 SLE groups. Compared with the inactive SLE group, the CD4+PD-1+T lymphocyte(t=6.03, P<0.001) and CD8+PD-1+ T lymphocyte percentage(t=3.22, P=0.003) had significantly increased and CD4+CTLA-4+ T lymphocyte(t=3.03, P=0.01) and CD8+CTLA-4+ T lymphocyte percentage(t=3.41, P=0.002) had decreased in the active SLE group. PD-1 and CTLA-4 were negative connected with each other(r=-0.85, r=-0.78, all P<0.001). Conclusions PD-1 and CTLA-4 play a very important role in the development of SLE. The expression of PD-1 and CTLA-4 might be expected to be a new therapeutic target of SLE through a certain way.