摘要
目的研究重组抗肿瘤坏死因子-α（TNF-α）人鼠嵌合单克隆抗体（anti—TNF rcMAb）对类风湿关节炎（RA）患者治疗效果及对患者外周血Th1、Th17、调节性T细胞影响。方法50例经严格筛选的RA患者按随机分配原则分为2组。联合治疗组（40例），给予anti-TNF rcMAb（3mg／kg）＋甲氨蝶呤治疗；对照组（10例）单独接受甲氨蝶呤治疗，分别于0、2、6、14周给药，于0、18周分别观察联合治疗组与对照组的相关临床指标的变化，在相应观察点做ACR20、50、70评分。同时，对比外周血中Th1、Th17、调节性T细胞的表达情况及相关转录因子T-bet、维甲酸相关孤核受体（ROR）C、叉头状转录因子3（Foxp3）的mRNA表达水平变化。采用t检验和χ^2检验或Ridit作统计学分析。结果治疗前后，联合治疗组ACR20、50、70较对照组均有所改善，尤其ACR20改善程度与对照组相比，差异有统计学意义（Z=1．671，P=0．00094）。联合治疗组患者外周血Th17细胞无显著变化[（0周（1．1±0．6）％；18周（1．1±0．3）％]、Th1细胞比例降低[0周（7．1±3．9）％；18周（4．2±2．8）％]，调节性T细胞比例明显升高[0周（91．5±0．8）％；18周（3．0±0．6）％，t=2．301，P=0．048]；对照组Th1比例下降[0周（9．1±3．1）％；18周（5．8±2．6）％]，调节性T细胞比例略升高[0周（1．2±0．6％）；18周（2．2±0．6）％]。2组Th17、Th1细胞的转录因子RORC、T-bet mRNA表达水平降低，调节性T细胞转录因子Foxp3的表达水平均升高。结论anti-TNF rcMAb联合甲氨蝶呤治疗对RA患者疗效显著，可能通过影响患者外周血Th细胞亚群发挥其治疗作用。
Objective To explore the effect of anti-TNF rcMAb in the treatment of patients with rheumatoid arthritis （RA） and its effect on peripheral blood Th1, Th17 and Treg cells. Methods Fifty rigorously screened RA patients were randomly divided to the therapy group （n=40） who received the com- bined treatment of anti-TNF rcMAb and MTX, and control group （n=10） who were given MTX along with placebo, both at week 0, 2, 6, and 14. The clinical data of the two groups were observed and accessed respectively at week 0 and 18. In addition, the percentage of Th1, Th17, Treg cells in the peripheral blood and the relative gene expressions of transcription factors T-bet, RORC, Foxp3 in these patients were also observed respectively before and after treatment. We used t inspection and χ^2 inspection as the statistical analysis methods in conducting this study. Results Comparing with the control group, more patients achieved ACR20, ACR50 and ACR70 response in the combined therapy group （Z=1.671 ,P=0.000 94）. The percentage of peripheral blood Th1 cells decreased [week 0： （7.1±3.9）%; week 18： （4.2±2.8）%] and the percentage of Treg cells obviously increased [week 0： （1.5±0.8）%; week 18： （3.0±0.6）%, t=2.301, P=0.048] in the combined therapy recipients, while the percentage of Th1 cells fell [week 0： （9.1±3.1）%; week 18： （5.8± 2.6）%] and that of Treg cells slightly increased [week 0： （1.2±0.6）%; week 18： （2.2±0.6）%] in the controls. The mRNA expressions of RORC and T-bet, the transcription factors of Th17 and Th1, were decreased respectively and that of Foxp3, the transcription factor of Treg, were elevated in both groups. Conclusion The combined therapy of anti-TNF rcMAb and MTX is very effective in RA patients. Good outcome is likely achieved by modifying the peripheral blood Th cell subsets in patients with RA.
出处
《中华风湿病学杂志》
CAS
CSCD
北大核心
2012年第7期481-485,共5页
Chinese Journal of Rheumatology
基金
上海市科学委员会自然科学基金（10ZR1422500）
