類風濕關(guān)節(jié)炎患者外周血Th17和調(diào)節(jié)性T細胞的絕對數(shù)量及小劑量IL-2對其影響
發(fā)布時間：2018-07-31 10:01
【摘要】：目的:1.類風濕關(guān)節(jié)炎(RA)患者和健康人外周血淋巴細胞亞群的比較;2.比較RA患者及健康人外周血Th17和Treg細胞百分數(shù)和絕對數(shù)及其比值的差異,并按疾病活動度評分(DAS28)將其分為疾病緩解組(DAS282.6)、低活動組(2.6~3.2)、中活動組(3.2~5.1)、高活動組(5.1),比較各組與健康人外周血Th17和Treg細胞及其比值的差異;3.長期應用傳統(tǒng)的改善病情抗風濕藥(DMARDS)治療對RA外周血Th17和Treg細胞及其比值的影響;4.分析RA外周血Th17和Treg細胞與疾病活動指標(DAS28、ESR、SJC、TJC)的相關(guān)性;5.小劑量IL-2對RA外周血Th17和Treg細胞及其比值的影響。方法:1.選取342例RA患者和93例健康人采集其外周血用流式細胞技術(shù)檢測外周血淋巴細胞亞群及Th17和Treg細胞百分數(shù)及絕對計數(shù),并收集臨床資料包括性別、年齡、病程、壓痛關(guān)節(jié)數(shù)(TJC)、腫脹關(guān)節(jié)數(shù)(SJC)、血沉(ESR)、C反應蛋白(CRP)、DAS28評分等;2.比較未用藥物治療的75例RA患者和健康人外周血中總T、總B、Th、CD3+CD8+T及NK細胞,評估RA患者的免疫功能;3.取CD4、CD25兩標標記的Treg細胞絕對數(shù)和百分數(shù)與CD4、CD25及Foxp3三標標記的Treg細胞比較,探討哪種標記方法更能有效地評估Treg細胞的狀態(tài);4.按DAS28評分對342例患者分層,比較不同疾病活動組與健康對照組Th17、Treg細胞絕對計數(shù),分析不同疾病狀態(tài)下Th17和Treg的分布情況;5.151例長期應用DMARDS治療的RA患者與未用藥物治療的75例患者比較Th17、Treg細胞的絕對計數(shù),評估藥物對兩個細胞的影響;6.對基線水平Th17、Treg細胞絕對數(shù)與CRP、ESR、TJC、SJC、DAS28評分分別行相關(guān)性分析,分析其與疾病狀態(tài)的關(guān)系;7.選取112例RA患者給予短期小劑量IL-2治療后,比較治療前后Th17、Treg細胞的絕對數(shù),評價小劑量IL-2對兩個細胞的影響。結(jié)果:1.未用藥RA患者與健康人相比,總T、總B、Th、CD3+CD8+T細胞均無統(tǒng)計學差異,而RA患者NK細胞明顯低于健康對照組;2.RA患者及健康對照組中CD4+CD25+Treg細胞絕對數(shù)無統(tǒng)計學差異,而RA患者中CD4+CD25+FOXp3+Treg細胞絕對數(shù)明顯低于健康對照組(P0.05);3.在RA不同疾病活動分層中,Treg細胞絕對數(shù)均低于健康對照組,其中DAS285.1組Treg細胞絕對數(shù)與健康人的差異有統(tǒng)計學意義。在RA不同疾病活動分層中,Th17細胞絕對數(shù)與對照組無統(tǒng)計學差異。Th17/Treg在DAS283.2的兩個水平組中均明顯高于對照組;4.Th17和Treg細胞絕對數(shù)在DMARDS組和無DMARDS組間比較均無統(tǒng)計學差異;5.Treg細胞絕對數(shù)與ESR及DAS28-ESR呈負相關(guān)性(P0.05),而Th17與上述兩個指標均無明顯相關(guān)性;6.IL-2治療后,Th17、Treg細胞絕對數(shù)較前升高且有統(tǒng)計學意義,Treg細胞絕對數(shù)升高更明顯,而Th17/Treg與治療前相比明顯降低。結(jié)論:1.與健康人相比,RA患者更易發(fā)生感染;2.CD4、CD25及Foxp3三標標記更能有效的評估Treg細胞數(shù)量;3.DMARDS對外周血Th17及Treg絕對數(shù)無明顯影響;4.Treg細胞數(shù)量減少引起免疫耐受缺陷可能是RA發(fā)生、發(fā)展的重要原因;5.Treg細胞絕對數(shù)可能作為評估類風濕關(guān)節(jié)炎疾病活動的一個預測指標;6.應用小劑量IL-2可以促進Th17、Treg細胞的增殖,并且能更加有效的增加Treg細胞數(shù)量,從而使Th17/Treg恢復平衡狀態(tài)。
[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.
【學位授予單位】：山西醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R593.22
本文編號：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.
【學位授予單位】：山西醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R593.22
【參考文獻】
相關(guān)期刊論文 前1條
1 李小峰;李雪飛;;上下臺階策略在解決類風濕關(guān)節(jié)炎治療過程中減藥停藥的有效方法初探[J];中華風濕病學雜志;2014年01期
，本文編號：2155234
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