共信号分子CD28、ICOS、PD-1、CTLA-4在类风湿关节炎的表达水平及意义
发布时间：2018-09-08 11:35
【摘要】：目的:为探讨共信号分子CD28、ICOS、PD-1、CTLA-4在类风湿关节炎的发病机制及意义,本实验通过流式细胞术检测四种共信号分子在类风湿关节炎患者外周血CD4+T细胞上的表达水平,并通过酶联免疫吸附测定检测sCD86、sICOS、sPD-1、sCTLA-4在类风湿关节炎患者血浆中的表达水平,同时与DAS28评分进行相关性分析。方法:(1)收集63例类风湿关节炎患者(其中活动期43例,稳定期20例)和30例健康对照者的外周血标本,通过流式细胞术检测共信号分子CD28、ICOS、PD-1、CTLA-4在类风湿关节炎患者活动期、稳定期及健康对照者外周血CD4+T细胞上的表达水平。(2)收集64例类风湿关节炎患者(其中活动期39例、稳定期25例)和20例健康对照者的血浆,通过酶联免疫吸附分别测定血浆中sCD86、sICOS、sPD-1、sCTLA-4在类风湿关节炎患者活动期、稳定期及健康对照者的表达水平。(3)将上述共信号分子的表达水平与DAS28评分进行Spearman相关性分析。结果:(1)流式细胞术分析结果显示:在类风湿关节炎患者中,活动期组外周血CD4+T细胞上CD28、ICOS、PD-1的表达水平与健康对照组相比,差异均有统计学意义(P0.01;P0.05;P0.01),且均呈高表达;活动期组CD28、ICOS、PD-1的表达水平与稳定期组相比,差异均无统计学意义(P0.05;P0.05;P0.05);活动期组与健康对照组、稳定期组相比,外周血CD4+T细胞上CTLA-4的表达水平差异均无统计学意义(P0.05;P0.05)。(2)酶联免疫吸附测定分析结果显示:类风湿关节炎患者活动期组血浆中sCD86、sPD-1、sCTLA-4的表达水平与健康对照组相比差异均有统计学意义,均呈高表达(P0.05;P0.01;P0.01);活动期组血浆中sICOS的表达水平与健康对照组相比差异无统计学意义(P0.05);其中活动期组血浆中sPD-1、sCTLA-4的表达水平较稳定期组升高,差异有统计学意义(P0.01;P0.01),而sCD86、sICOS在活动期组、稳定期组血浆中的表达水平差异均无统计学意义(P0.05;P0.05)。(3)类风湿关节炎患者活动期组外周血CD4+T细胞上ICOS的表达水平与DAS28评分呈正相关,CD28、PD-1、CTLA-4的表达水平与DAS28评分无相关性;类风湿关节炎患者活动期组血浆中sPD-1、sCTLA-4的表达水平与DAS28评分呈正相关,sCD86、sICOS的表达水平与DAS28评分无相关性。结论:共信号分子CD28、CD28的配体CD86、ICOS、PD-1和CTLA-4在类风湿关节炎患者外周血CD4+T细胞上及血浆中表达异常,推测其在类风湿关节炎的发病机制中可能发挥作用。其中sPD-1、sCTLA-4在RA血浆中的表达水平与DAS28评分呈正相关,提示其与RA疾病活动性相关,可能成为疾病活动监测的指标。
[Abstract]:Objective: to investigate the pathogenesis and significance of co-signal molecule CD28,ICOS,PD-1,CTLA-4 in rheumatoid arthritis (RA), the expression of four co-signaling molecules in peripheral blood CD4 T cells of patients with rheumatoid arthritis was detected by flow cytometry. The expression of sCD86,sICOS,sPD-1,sCTLA-4 in the plasma of patients with rheumatoid arthritis was detected by enzyme-linked immunosorbent assay (Elisa), and the correlation with DAS28 score was analyzed. Methods: (1) Peripheral blood samples of 63 patients with rheumatoid arthritis (43 active, 20 stable) and 30 healthy controls were collected. The co-signal molecule CD28,ICOS,PD-1,CTLA-4 was detected by flow cytometry in active stage of rheumatoid arthritis. The expression of CD4 T cells in peripheral blood of stable and healthy controls. (2) Plasma samples were collected from 64 patients with rheumatoid arthritis (39 active, 25 stable) and 20 healthy controls. The expression of sCD86,sICOS,sPD-1,sCTLA-4 in patients with rheumatoid arthritis (RA) was measured by Elisa. (3) the Spearman correlation analysis was performed between the expression of co-signal molecules and DAS28 score in patients with rheumatoid arthritis. Results: (1) the results of flow cytometry showed that the expression of CD28,ICOS,PD-1 on peripheral blood CD4 T cells in active group was significantly higher than that in healthy control group (P0.01, P0.05, P0.01). There was no significant difference in the expression of CD28,ICOS,PD-1 between the active group and the stable group (P0.05, P0.05, P0.05), while the expression of CD28,ICOS,PD-1 in the active phase group was higher than that in the healthy control group and the stable phase group, while in the active phase group, there was no significant difference between the two groups. There was no significant difference in the expression of CTLA-4 on peripheral blood CD4 T cells (P0.05P 0.05). (2). The results of enzyme-linked immunosorbent assay (Elisa) showed that the expression of sCD86,sPD-1,sCTLA-4 in plasma of active stage patients with rheumatoid arthritis was different from that of healthy controls. Are statistically significant, There was no significant difference in the expression of sICOS between the active group and the healthy control group (P0.05), and the expression level of sPD-1,sCTLA-4 in the active phase group was higher than that in the stable phase group (P 0.01), while the expression level of sCD86,sICOS in the active phase group was significantly higher than that in the stable phase group (P0.01), while in the active phase group, the expression level of sCD86,sICOS in the active phase group was significantly higher than that in the stable phase group (P0.01). There was no significant difference in plasma expression level between stable group and control group (P0.05P 0.05). (3). The expression of ICOS on peripheral blood CD4 T cells in active phase of rheumatoid arthritis patients was positively correlated with DAS28 score. There was no correlation between the expression level of CD28PD-1 CTLA-4 and DAS28 score. There was no correlation between the expression of sPD-1,sCTLA-4 in plasma and DAS28 score in active patients with rheumatoid arthritis. There was no correlation between the expression level of sCD86 and DAS28 score. Conclusion: the expression of CD86,ICOS,PD-1 and CTLA-4 in peripheral blood CD4 T cells and plasma of patients with rheumatoid arthritis (RA) is abnormal, which suggests that CD86,ICOS,PD-1 and CTLA-4 may play a role in the pathogenesis of rheumatoid arthritis. The expression of sPD-1,sCTLA-4 in the plasma of RA was positively correlated with the DAS28 score, which suggested that the expression level of sPD-1,sCTLA-4 was correlated with the disease activity of RA, and might become an indicator of disease activity monitoring.
【学位授予单位】：川北医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R593.22
本文编号：2230399
[Abstract]:Objective: to investigate the pathogenesis and significance of co-signal molecule CD28,ICOS,PD-1,CTLA-4 in rheumatoid arthritis (RA), the expression of four co-signaling molecules in peripheral blood CD4 T cells of patients with rheumatoid arthritis was detected by flow cytometry. The expression of sCD86,sICOS,sPD-1,sCTLA-4 in the plasma of patients with rheumatoid arthritis was detected by enzyme-linked immunosorbent assay (Elisa), and the correlation with DAS28 score was analyzed. Methods: (1) Peripheral blood samples of 63 patients with rheumatoid arthritis (43 active, 20 stable) and 30 healthy controls were collected. The co-signal molecule CD28,ICOS,PD-1,CTLA-4 was detected by flow cytometry in active stage of rheumatoid arthritis. The expression of CD4 T cells in peripheral blood of stable and healthy controls. (2) Plasma samples were collected from 64 patients with rheumatoid arthritis (39 active, 25 stable) and 20 healthy controls. The expression of sCD86,sICOS,sPD-1,sCTLA-4 in patients with rheumatoid arthritis (RA) was measured by Elisa. (3) the Spearman correlation analysis was performed between the expression of co-signal molecules and DAS28 score in patients with rheumatoid arthritis. Results: (1) the results of flow cytometry showed that the expression of CD28,ICOS,PD-1 on peripheral blood CD4 T cells in active group was significantly higher than that in healthy control group (P0.01, P0.05, P0.01). There was no significant difference in the expression of CD28,ICOS,PD-1 between the active group and the stable group (P0.05, P0.05, P0.05), while the expression of CD28,ICOS,PD-1 in the active phase group was higher than that in the healthy control group and the stable phase group, while in the active phase group, there was no significant difference between the two groups. There was no significant difference in the expression of CTLA-4 on peripheral blood CD4 T cells (P0.05P 0.05). (2). The results of enzyme-linked immunosorbent assay (Elisa) showed that the expression of sCD86,sPD-1,sCTLA-4 in plasma of active stage patients with rheumatoid arthritis was different from that of healthy controls. Are statistically significant, There was no significant difference in the expression of sICOS between the active group and the healthy control group (P0.05), and the expression level of sPD-1,sCTLA-4 in the active phase group was higher than that in the stable phase group (P 0.01), while the expression level of sCD86,sICOS in the active phase group was significantly higher than that in the stable phase group (P0.01), while in the active phase group, the expression level of sCD86,sICOS in the active phase group was significantly higher than that in the stable phase group (P0.01). There was no significant difference in plasma expression level between stable group and control group (P0.05P 0.05). (3). The expression of ICOS on peripheral blood CD4 T cells in active phase of rheumatoid arthritis patients was positively correlated with DAS28 score. There was no correlation between the expression level of CD28PD-1 CTLA-4 and DAS28 score. There was no correlation between the expression of sPD-1,sCTLA-4 in plasma and DAS28 score in active patients with rheumatoid arthritis. There was no correlation between the expression level of sCD86 and DAS28 score. Conclusion: the expression of CD86,ICOS,PD-1 and CTLA-4 in peripheral blood CD4 T cells and plasma of patients with rheumatoid arthritis (RA) is abnormal, which suggests that CD86,ICOS,PD-1 and CTLA-4 may play a role in the pathogenesis of rheumatoid arthritis. The expression of sPD-1,sCTLA-4 in the plasma of RA was positively correlated with the DAS28 score, which suggested that the expression level of sPD-1,sCTLA-4 was correlated with the disease activity of RA, and might become an indicator of disease activity monitoring.
【学位授予单位】：川北医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R593.22
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