类风湿关节炎患者外周血Th17和调节性T细胞的绝对数量及小剂量IL-2对其影响
发布时间：2018-07-31 10:01
【摘要】：目的:1.类风湿关节炎(RA)患者和健康人外周血淋巴细胞亚群的比较;2.比较RA患者及健康人外周血Th17和Treg细胞百分数和绝对数及其比值的差异,并按疾病活动度评分(DAS28)将其分为疾病缓解组(DAS282.6)、低活动组(2.6~3.2)、中活动组(3.2~5.1)、高活动组(5.1),比较各组与健康人外周血Th17和Treg细胞及其比值的差异;3.长期应用传统的改善病情抗风湿药(DMARDS)治疗对RA外周血Th17和Treg细胞及其比值的影响;4.分析RA外周血Th17和Treg细胞与疾病活动指标(DAS28、ESR、SJC、TJC)的相关性;5.小剂量IL-2对RA外周血Th17和Treg细胞及其比值的影响。方法:1.选取342例RA患者和93例健康人采集其外周血用流式细胞技术检测外周血淋巴细胞亚群及Th17和Treg细胞百分数及绝对计数,并收集临床资料包括性别、年龄、病程、压痛关节数(TJC)、肿胀关节数(SJC)、血沉(ESR)、C反应蛋白(CRP)、DAS28评分等;2.比较未用药物治疗的75例RA患者和健康人外周血中总T、总B、Th、CD3+CD8+T及NK细胞,评估RA患者的免疫功能;3.取CD4、CD25两标标记的Treg细胞绝对数和百分数与CD4、CD25及Foxp3三标标记的Treg细胞比较,探讨哪种标记方法更能有效地评估Treg细胞的状态;4.按DAS28评分对342例患者分层,比较不同疾病活动组与健康对照组Th17、Treg细胞绝对计数,分析不同疾病状态下Th17和Treg的分布情况;5.151例长期应用DMARDS治疗的RA患者与未用药物治疗的75例患者比较Th17、Treg细胞的绝对计数,评估药物对两个细胞的影响;6.对基线水平Th17、Treg细胞绝对数与CRP、ESR、TJC、SJC、DAS28评分分别行相关性分析,分析其与疾病状态的关系;7.选取112例RA患者给予短期小剂量IL-2治疗后,比较治疗前后Th17、Treg细胞的绝对数,评价小剂量IL-2对两个细胞的影响。结果:1.未用药RA患者与健康人相比,总T、总B、Th、CD3+CD8+T细胞均无统计学差异,而RA患者NK细胞明显低于健康对照组;2.RA患者及健康对照组中CD4+CD25+Treg细胞绝对数无统计学差异,而RA患者中CD4+CD25+FOXp3+Treg细胞绝对数明显低于健康对照组(P0.05);3.在RA不同疾病活动分层中,Treg细胞绝对数均低于健康对照组,其中DAS285.1组Treg细胞绝对数与健康人的差异有统计学意义。在RA不同疾病活动分层中,Th17细胞绝对数与对照组无统计学差异。Th17/Treg在DAS283.2的两个水平组中均明显高于对照组;4.Th17和Treg细胞绝对数在DMARDS组和无DMARDS组间比较均无统计学差异;5.Treg细胞绝对数与ESR及DAS28-ESR呈负相关性(P0.05),而Th17与上述两个指标均无明显相关性;6.IL-2治疗后,Th17、Treg细胞绝对数较前升高且有统计学意义,Treg细胞绝对数升高更明显,而Th17/Treg与治疗前相比明显降低。结论:1.与健康人相比,RA患者更易发生感染;2.CD4、CD25及Foxp3三标标记更能有效的评估Treg细胞数量;3.DMARDS对外周血Th17及Treg绝对数无明显影响;4.Treg细胞数量减少引起免疫耐受缺陷可能是RA发生、发展的重要原因;5.Treg细胞绝对数可能作为评估类风湿关节炎疾病活动的一个预测指标;6.应用小剂量IL-2可以促进Th17、Treg细胞的增殖,并且能更加有效的增加Treg细胞数量,从而使Th17/Treg恢复平衡状态。
[Abstract]:Objective: To compare the peripheral blood lymphocyte subsets of 1. rheumatoid arthritis (RA) patients and healthy people. 2. compare the difference of the percentage and absolute number of Th17 and Treg cells in peripheral blood of RA and healthy people, and divide them into the disease remission group (DAS282.6), the low activity group (2.6~3.2), and the middle activity group (3.2~5.1), according to the disease activity score (DAS28). The high activity group (5.1) compared the difference of Th17 and Treg cells and their ratio in peripheral blood of healthy people. 3. the effect of traditional treatment on the Th17 and Treg cells of RA peripheral blood and the ratio of Th17 and Treg cells in the treatment of disease resistant rheumatic drugs (DMARDS); and 4. to analyze the correlation between Th17 and Treg cells in the peripheral blood of RA and the index of disease activity (DAS28, ESR, SJC, and SJC); 5. The effect of dose IL-2 on Th17 and Treg cells and their ratio in peripheral blood of RA. Methods: 1. the percentage and absolute count of peripheral blood lymphocyte subsets and Th17 and Treg cells were detected by flow cytometry in 342 cases of RA and 93 healthy people, and the clinical data included sex, age, course of disease, number of pressure pain joint (TJC), and swelling. The number of bulging joints (SJC), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), DAS28 score, etc.; 2. compared the total T, total B, Th, CD3+CD8+T and NK cells in the peripheral blood of 75 patients with untreated RA and healthy people, to evaluate the immune function of the RA patients; 3. In comparison, which method could be used to evaluate the status of Treg cells more effectively; 4. the 342 cases were stratified by DAS28 score, and the absolute count of Th17 and Treg cells in different disease activities group and healthy control group were compared, and the distribution of Th17 and Treg in different disease states was analyzed; 5.151 cases of RA patients with long-term application of DMARDS treatment were treated with unused drugs. 75 patients were compared with the absolute count of Th17 and Treg cells to assess the effect of drugs on two cells; 6. to baseline level Th17, the absolute number of Treg cells was correlated with CRP, ESR, TJC, SJC, and DAS28 scores, respectively, to analyze the relationship with the state of disease; 7. select 112 cases of RA patients to give short dose IL-2 treatment and compare Th1 before and after treatment. 7, the absolute number of Treg cells, evaluation of the effect of small dose of IL-2 on two cells. Results: 1. the total T, total B, Th, CD3+CD8+T cells were not statistically significant compared with healthy people in 1. untreated patients, and NK cells in RA patients were significantly lower than those in the healthy control group; the absolute number of CD4+CD25+Treg cells in 2.RA patients and healthy controls was not statistically significant, while RA patients had no statistical difference. The absolute number of CD4+CD25+FOXp3+Treg cells was significantly lower than that of the healthy control group (P0.05); 3. the absolute number of Treg cells in the activity stratification of RA was lower than that in the healthy control group, and the absolute number of Treg cells in the DAS285.1 group was statistically significant. The absolute number of Th17 cells in the RA disease activity stratification was no more than that of the control group. The statistical difference.Th17/Treg was significantly higher in the two level groups of DAS283.2 than in the control group; the absolute number of 4.Th17 and Treg cells was not statistically significant between the DMARDS and the DMARDS groups; the absolute number of 5.Treg cells was negatively correlated with ESR and DAS28-ESR (P0.05), while Th17 was not significantly correlated with the above two indexes. 7, the absolute number of Treg cells was higher and statistically significant, the absolute number of Treg cells increased significantly, and Th17/Treg was significantly lower than that before treatment. Conclusion: 1. compared with healthy people, RA patients are more susceptible to infection; 2.CD4, CD25 and Foxp3 three markers are more effective in evaluating the number of Treg cells; 3.DMARDS external Th17 and Treg absolute number is not Obviously, the decrease in the number of 4.Treg cells may be an important reason for the development of RA, and the absolute number of 5.Treg cells may be a predictor for evaluating the activity of rheumatoid arthritis; 6. the use of low dose IL-2 can promote the proliferation of Th17, Treg cells, and increase the number of Treg cells more effectively. Thus, the equilibrium state of the Th17/Treg is restored.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R593.22
本文编号：2155234
[Abstract]:Objective: To compare the peripheral blood lymphocyte subsets of 1. rheumatoid arthritis (RA) patients and healthy people. 2. compare the difference of the percentage and absolute number of Th17 and Treg cells in peripheral blood of RA and healthy people, and divide them into the disease remission group (DAS282.6), the low activity group (2.6~3.2), and the middle activity group (3.2~5.1), according to the disease activity score (DAS28). The high activity group (5.1) compared the difference of Th17 and Treg cells and their ratio in peripheral blood of healthy people. 3. the effect of traditional treatment on the Th17 and Treg cells of RA peripheral blood and the ratio of Th17 and Treg cells in the treatment of disease resistant rheumatic drugs (DMARDS); and 4. to analyze the correlation between Th17 and Treg cells in the peripheral blood of RA and the index of disease activity (DAS28, ESR, SJC, and SJC); 5. The effect of dose IL-2 on Th17 and Treg cells and their ratio in peripheral blood of RA. Methods: 1. the percentage and absolute count of peripheral blood lymphocyte subsets and Th17 and Treg cells were detected by flow cytometry in 342 cases of RA and 93 healthy people, and the clinical data included sex, age, course of disease, number of pressure pain joint (TJC), and swelling. The number of bulging joints (SJC), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), DAS28 score, etc.; 2. compared the total T, total B, Th, CD3+CD8+T and NK cells in the peripheral blood of 75 patients with untreated RA and healthy people, to evaluate the immune function of the RA patients; 3. In comparison, which method could be used to evaluate the status of Treg cells more effectively; 4. the 342 cases were stratified by DAS28 score, and the absolute count of Th17 and Treg cells in different disease activities group and healthy control group were compared, and the distribution of Th17 and Treg in different disease states was analyzed; 5.151 cases of RA patients with long-term application of DMARDS treatment were treated with unused drugs. 75 patients were compared with the absolute count of Th17 and Treg cells to assess the effect of drugs on two cells; 6. to baseline level Th17, the absolute number of Treg cells was correlated with CRP, ESR, TJC, SJC, and DAS28 scores, respectively, to analyze the relationship with the state of disease; 7. select 112 cases of RA patients to give short dose IL-2 treatment and compare Th1 before and after treatment. 7, the absolute number of Treg cells, evaluation of the effect of small dose of IL-2 on two cells. Results: 1. the total T, total B, Th, CD3+CD8+T cells were not statistically significant compared with healthy people in 1. untreated patients, and NK cells in RA patients were significantly lower than those in the healthy control group; the absolute number of CD4+CD25+Treg cells in 2.RA patients and healthy controls was not statistically significant, while RA patients had no statistical difference. The absolute number of CD4+CD25+FOXp3+Treg cells was significantly lower than that of the healthy control group (P0.05); 3. the absolute number of Treg cells in the activity stratification of RA was lower than that in the healthy control group, and the absolute number of Treg cells in the DAS285.1 group was statistically significant. The absolute number of Th17 cells in the RA disease activity stratification was no more than that of the control group. The statistical difference.Th17/Treg was significantly higher in the two level groups of DAS283.2 than in the control group; the absolute number of 4.Th17 and Treg cells was not statistically significant between the DMARDS and the DMARDS groups; the absolute number of 5.Treg cells was negatively correlated with ESR and DAS28-ESR (P0.05), while Th17 was not significantly correlated with the above two indexes. 7, the absolute number of Treg cells was higher and statistically significant, the absolute number of Treg cells increased significantly, and Th17/Treg was significantly lower than that before treatment. Conclusion: 1. compared with healthy people, RA patients are more susceptible to infection; 2.CD4, CD25 and Foxp3 three markers are more effective in evaluating the number of Treg cells; 3.DMARDS external Th17 and Treg absolute number is not Obviously, the decrease in the number of 4.Treg cells may be an important reason for the development of RA, and the absolute number of 5.Treg cells may be a predictor for evaluating the activity of rheumatoid arthritis; 6. the use of low dose IL-2 can promote the proliferation of Th17, Treg cells, and increase the number of Treg cells more effectively. Thus, the equilibrium state of the Th17/Treg is restored.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R593.22
【参考文献】
相关期刊论文 前1条
1 李小峰;李雪飞;;上下台阶策略在解决类风湿关节炎治疗过程中减药停药的有效方法初探[J];中华风湿病学杂志;2014年01期
，本文编号：2155234
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