摘要
目的研究艾拉莫德对RA患者的临床疗效及其在治疗RA中的免疫调节作用机制。方法应用临床随机对照试验探究其临床疗效，流式细胞术检测治疗前后患者外周血辅助性T细胞（Th）1、Th17和调节性T细胞比例变化，实时定量PCR方法检测相关转录因子的表达水平，探讨其免疫调节作用，采用t检验、x2检验、秩和检验对数据进行统计学分析。结果经艾拉莫德治疗24周后，患者临床症状改善明显，ACR20、ACR50、ACR70达标率分别为50％、20％、15％，远高于对照组25％、12％、6％，差异具有统计学意义（z=-2．216，P=0．027）；外周血中Th1、Th17细胞亚群的比例有所下降[Th1：0周（26．5±8．0）％，24周（14．2±7.3）％，P〈0．01；Th17：0周（1．7±0．7）％，24周（1．3±0．4）％，P〈0．05]，调节性T细胞亚群比例有所上升[0周（6．8±1．6）％，24周（8．9±2．9）％，P〈0．05]，它们相应的转录因子也呈相同趋势。结论艾拉莫德能够有效改善RA患者的临床病情，且可通过降低T细胞亚群中Th1、Th17比例，升高调节性T细胞比例，并下调Th17细胞的关键转录因子孤儿核受体（RORC）的表达而发挥作用。
Objective Rheumatoid arthritis （RA） is a systemic autoimmune disease, which mainly involves joints across the body, resulting in joint stiffness and loss of daily activity. Recent evidence suggests that numerous self-reacting T cells, including Thl and ThlT, infiltrate the synovium in RA patients, accompanied by functionally-compromised. Treg. Iguratimod, a new small molecule with anti-inflammatory and immunomodulatory effects, has shown curative effects in animal models of arthritis, In this study, we aimed to test the clinical effects of Iguratimed＇s on RA patientsand its role in immunoregulation. Methods We examined the clinical effects of iguratimod on RA patients in a random Controlled clinical trials and analyzed its effects on Thl, Th17 and Treg as well as their associated cytokines and transcription factors by flow cytometry and real-time polymerase chain reaction （PCR）. Then t-test, chi-square test and rank sum test were used to conduct statistical analysis. Results Our results revealed that iguratimod therapy provided significantly greater clinical benefit [ACR20, ACR50, ACR70 reached 50%, 20%, 15% respectively in iguratimed treatment group, Z=-2.210,P=0.027] than placebo group with the reduction of Thl and Th17 but increment of Treg after ignratimod treatment [Thl： week 0 （26.5±8.0）%, week 24 （14.2±7.3）%, P〈0.01; Th17：week 0 （1.7±0.7）%, week 24 （1.3±0.4）%,〈0.05; Treg： week 0 （6.8±1.6）%, week 24 （8.9±2.9）%, P〈0.05], which was statistically significant. Conclusion Our results provide theoretical and clinical based evidence for the impact of iguratimod on immunomodulation of RA.
出处
《中华风湿病学杂志》
CAS
CSCD
北大核心
2016年第2期93-99,共7页
Chinese Journal of Rheumatology
基金
国家自然科学基金（81302569）
上海市卫生局基金（20124196,20124229）
上海市教育委员会基金（14YZ042）
上海交通大学医工交叉基金（YG2014MS77）
上海交通大学医学院大学生科创项目（2013004）和第七期国家级大学生创新训练项目（201410248061）
上海交通大学医学院RBL项目（2013RB002）
关键词
关节炎
类风湿
艾拉莫德
治疗结果
免疫调节
T淋巴细胞
辅助诱导
Arthritis, rheumatoid
Iguratimod
Treatment outcome
Immunoregulation
T-lymphocytes, helper-inducer
