中华风湿病学杂志
中華風濕病學雜誌
중화풍습병학잡지
CHINESE JOURNAL OF RHEUMATOLOGY
2012年
6期
383-387
,共5页
关节炎,类风湿%白细胞介素17%重组人CTLA-4抗体融合蛋白%FoxP3
關節炎,類風濕%白細胞介素17%重組人CTLA-4抗體融閤蛋白%FoxP3
관절염,류풍습%백세포개소17%중조인CTLA-4항체융합단백%FoxP3
Arthritis,rheumatoid%Interleukin-17%rhCTLA-4Ig%FoxP3
目的 探讨应用重组人细胞毒T淋巴细胞相关抗原(CTLA)-4抗体融合蛋白(rhCTLA-41g)治疗类风湿关节炎(RA)患者的临床疗效及对患者外周血辅助性T细胞17(Th17)和调节性T细胞的影响.方法 48例处于活动期的RA患者按1:1的比例随机分为治疗组和对照组,治疗组接受12周的rhCTLA-4Ig(10mg/kg)治疗；对照组接受12周的安慰剂治疗.以美国风湿病学会RA20％改善标准(ACR20)及疾病活动指数(DAS)28观察临床疗效；同时用流式细胞术检测受试者外周血Th17的变化,反转录聚合酶链反应(RT-PCR)检测外周血单个核细胞中FoxP3表达水平的变化.采用t检验和x2检验进行统计学分析.结果 ①治疗后12周治疗组24例中18例达ACR20改善,达ACR20改善的患者比例为75％,对照组中有1例(4％)达ACR20改善,2组差异有统计学意义(x2=25.176,P＜0.01)；治疗后12周DAS28评分治疗组与对照组比较差异有统计学意义(分别为3.0±0.7,6.9±0.7,t=-12.39,P＜0.01).②治疗后治疗组RA患者外周血表达IL17A的单个核细胞为(0.22±0.20)％,对照组为(1.63±0.47)％,治疗组较对照组显著下降,差异有统计学意义(t=5.61,P＜0.05).③治疗组FoxP3 mRNA的表达(0.88±0.18)较对照组(0.24±0.05)明显增高,差异有统计学意义(t=7.56,P＜0.01).结论 rhCTLA-4Ig治疗RA临床表现和实验室指标明显改善,且外周血中TH17细胞及调节性T细胞的失衡程度有明显恢复.
目的 探討應用重組人細胞毒T淋巴細胞相關抗原(CTLA)-4抗體融閤蛋白(rhCTLA-41g)治療類風濕關節炎(RA)患者的臨床療效及對患者外週血輔助性T細胞17(Th17)和調節性T細胞的影響.方法 48例處于活動期的RA患者按1:1的比例隨機分為治療組和對照組,治療組接受12週的rhCTLA-4Ig(10mg/kg)治療；對照組接受12週的安慰劑治療.以美國風濕病學會RA20％改善標準(ACR20)及疾病活動指數(DAS)28觀察臨床療效；同時用流式細胞術檢測受試者外週血Th17的變化,反轉錄聚閤酶鏈反應(RT-PCR)檢測外週血單箇覈細胞中FoxP3錶達水平的變化.採用t檢驗和x2檢驗進行統計學分析.結果 ①治療後12週治療組24例中18例達ACR20改善,達ACR20改善的患者比例為75％,對照組中有1例(4％)達ACR20改善,2組差異有統計學意義(x2=25.176,P＜0.01)；治療後12週DAS28評分治療組與對照組比較差異有統計學意義(分彆為3.0±0.7,6.9±0.7,t=-12.39,P＜0.01).②治療後治療組RA患者外週血錶達IL17A的單箇覈細胞為(0.22±0.20)％,對照組為(1.63±0.47)％,治療組較對照組顯著下降,差異有統計學意義(t=5.61,P＜0.05).③治療組FoxP3 mRNA的錶達(0.88±0.18)較對照組(0.24±0.05)明顯增高,差異有統計學意義(t=7.56,P＜0.01).結論 rhCTLA-4Ig治療RA臨床錶現和實驗室指標明顯改善,且外週血中TH17細胞及調節性T細胞的失衡程度有明顯恢複.
목적 탐토응용중조인세포독T림파세포상관항원(CTLA)-4항체융합단백(rhCTLA-41g)치료류풍습관절염(RA)환자적림상료효급대환자외주혈보조성T세포17(Th17)화조절성T세포적영향.방법 48례처우활동기적RA환자안1:1적비례수궤분위치료조화대조조,치료조접수12주적rhCTLA-4Ig(10mg/kg)치료；대조조접수12주적안위제치료.이미국풍습병학회RA20％개선표준(ACR20)급질병활동지수(DAS)28관찰림상료효；동시용류식세포술검측수시자외주혈Th17적변화,반전록취합매련반응(RT-PCR)검측외주혈단개핵세포중FoxP3표체수평적변화.채용t검험화x2검험진행통계학분석.결과 ①치료후12주치료조24례중18례체ACR20개선,체ACR20개선적환자비례위75％,대조조중유1례(4％)체ACR20개선,2조차이유통계학의의(x2=25.176,P＜0.01)；치료후12주DAS28평분치료조여대조조비교차이유통계학의의(분별위3.0±0.7,6.9±0.7,t=-12.39,P＜0.01).②치료후치료조RA환자외주혈표체IL17A적단개핵세포위(0.22±0.20)％,대조조위(1.63±0.47)％,치료조교대조조현저하강,차이유통계학의의(t=5.61,P＜0.05).③치료조FoxP3 mRNA적표체(0.88±0.18)교대조조(0.24±0.05)명현증고,차이유통계학의의(t=7.56,P＜0.01).결론 rhCTLA-4Ig치료RA림상표현화실험실지표명현개선,차외주혈중TH17세포급조절성T세포적실형정도유명현회복.
Objective To discuss the therapeutic effect of recombinant human CTLA-4Ig fusion protein (rhCTLA-4Ig) on rheumatoid arthritis (RA) patients and the change of T helper cells 17 (Th1 7 ) and regulatory T (Treg) cells.Methods Forty-eight active RA patients were randomly divided into the treatment group and the control group.Treatment group received 12 weeks of infusions of rhCTLA-4Ig ( 10 mg/kg),while the control group received 12 weeks of infusions of placebo.The changes of expression levels of Th17cell were detected by flow cytometry.The changes of expression level of FoxP3 in monocytes of the peripheral blood were examined by RT-PCR.T test and x2 test were used for statistical analysis.Results ① Eighteen of 24 cases in treatment group showed good ACR20 changes after 12 weeks,the effective rate (75％) was significantly higher than that of the control group ( 1/24,4％ ).After treatment,DAS28 score of the treatment group (3.0±0.7) was significantly lower than that of the control group(6.9±0.7) (t=-12.39,P＜0.01 ).② Compared with the Th17 monocytes of the peripheral blood from active RA patients of treatment group after therapy (0.22±0.20)％,the Th17 monocytes of peripheral blood from active RA patients of the control group (1.63±0.47)％ were higher (t=5.61,P＜0.05 ).③ Compared with the FoxP3 mRNA of the control group (0.24±0.05),that of the treatment group (0.88±0.18) was significantly higher after therapy (t=7.56,P＜0.01 ).Conclusion The clinical parameters of RA patients have improved significantly after the treatment,and the Th17 and Treg cells balance is also restored after rhCTLA-4Ig therapy.
