類風(fēng)濕關(guān)節(jié)炎患者外周血Th17和調(diào)節(jié)性T細(xì)胞的絕對(duì)數(shù)量及小劑量IL-2對(duì)其影響
發(fā)布時(shí)間：2018-07-31 10:01
【摘要】：目的:1.類風(fēng)濕關(guān)節(jié)炎(RA)患者和健康人外周血淋巴細(xì)胞亞群的比較;2.比較RA患者及健康人外周血Th17和Treg細(xì)胞百分?jǐn)?shù)和絕對(duì)數(shù)及其比值的差異,并按疾病活動(dòng)度評(píng)分(DAS28)將其分為疾病緩解組(DAS282.6)、低活動(dòng)組(2.6~3.2)、中活動(dòng)組(3.2~5.1)、高活動(dòng)組(5.1),比較各組與健康人外周血Th17和Treg細(xì)胞及其比值的差異;3.長(zhǎng)期應(yīng)用傳統(tǒng)的改善病情抗風(fēng)濕藥(DMARDS)治療對(duì)RA外周血Th17和Treg細(xì)胞及其比值的影響;4.分析RA外周血Th17和Treg細(xì)胞與疾病活動(dòng)指標(biāo)(DAS28、ESR、SJC、TJC)的相關(guān)性;5.小劑量IL-2對(duì)RA外周血Th17和Treg細(xì)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(xì)胞技術(shù)檢測(cè)外周血淋巴細(xì)胞亞群及Th17和Treg細(xì)胞百分?jǐn)?shù)及絕對(duì)計(jì)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(yīng)蛋白(CRP)、DAS28評(píng)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(xì)胞,評(píng)估RA患者的免疫功能;3.取CD4、CD25兩標(biāo)標(biāo)記的Treg細(xì)胞絕對(duì)數(shù)和百分?jǐn)?shù)與CD4、CD25及Foxp3三標(biāo)標(biāo)記的Treg細(xì)胞比較,探討哪種標(biāo)記方法更能有效地評(píng)估Treg細(xì)胞的狀態(tài);4.按DAS28評(píng)分對(duì)342例患者分層,比較不同疾病活動(dòng)組與健康對(duì)照組Th17、Treg細(xì)胞絕對(duì)計(jì)數(shù),分析不同疾病狀態(tài)下Th17和Treg的分布情況;5.151例長(zhǎng)期應(yīng)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(xì)胞的絕對(duì)計(jì)數(shù),評(píng)估藥物對(duì)兩個(gè)細(xì)胞的影響;6.對(duì)基線水平Th17、Treg細(xì)胞絕對(duì)數(shù)與CRP、ESR、TJC、SJC、DAS28評(píng)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(xì)胞的絕對(duì)數(shù),評(píng)價(jià)小劑量IL-2對(duì)兩個(gè)細(xì)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(xì)胞均無(wú)統(tǒng)計(jì)學(xué)差異,而RA患者NK細(xì)胞明顯低于健康對(duì)照組;2.RA患者及健康對(duì)照組中CD4+CD25+Treg細(xì)胞絕對(duì)數(shù)無(wú)統(tǒng)計(jì)學(xué)差異,而RA患者中CD4+CD25+FOXp3+Treg細(xì)胞絕對(duì)數(shù)明顯低于健康對(duì)照組(P0.05);3.在RA不同疾病活動(dòng)分層中,Treg細(xì)胞絕對(duì)數(shù)均低于健康對(duì)照組,其中DAS285.1組Treg細(xì)胞絕對(duì)數(shù)與健康人的差異有統(tǒng)計(jì)學(xué)意義。在RA不同疾病活動(dòng)分層中,Th17細(xì)胞絕對(duì)數(shù)與對(duì)照組無(wú)統(tǒng)計(jì)學(xué)差異。Th17/Treg在DAS283.2的兩個(gè)水平組中均明顯高于對(duì)照組;4.Th17和Treg細(xì)胞絕對(duì)數(shù)在DMARDS組和無(wú)DMARDS組間比較均無(wú)統(tǒng)計(jì)學(xué)差異;5.Treg細(xì)胞絕對(duì)數(shù)與ESR及DAS28-ESR呈負(fù)相關(guān)性(P0.05),而Th17與上述兩個(gè)指標(biāo)均無(wú)明顯相關(guān)性;6.IL-2治療后,Th17、Treg細(xì)胞絕對(duì)數(shù)較前升高且有統(tǒng)計(jì)學(xué)意義,Treg細(xì)胞絕對(duì)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(biāo)標(biāo)記更能有效的評(píng)估Treg細(xì)胞數(shù)量;3.DMARDS對(duì)外周血Th17及Treg絕對(duì)數(shù)無(wú)明顯影響;4.Treg細(xì)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(xì)胞絕對(duì)數(shù)可能作為評(píng)估類風(fēng)濕關(guān)節(jié)炎疾病活動(dòng)的一個(gè)預(yù)測(cè)指標(biāo);6.應(yīng)用小劑量IL-2可以促進(jìn)Th17、Treg細(xì)胞的增殖,并且能更加有效的增加Treg細(xì)胞數(shù)量,從而使Th17/Treg恢復(fù)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(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R593.22
本文編號(hào)：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(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R593.22
【參考文獻(xiàn)】
相關(guān)期刊論文 前1條
1 李小峰;李雪飛;;上下臺(tái)階策略在解決類風(fēng)濕關(guān)節(jié)炎治療過(guò)程中減藥停藥的有效方法初探[J];中華風(fēng)濕病學(xué)雜志;2014年01期
，本文編號(hào)：2155234
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