Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, China.
Rheumatol Int. 2010 Nov;30(12):1553-7. doi: 10.1007/s00296-009-1179-x. Epub 2009 Oct 22.
Objective of the study is to assess the effects of adalimumab and MTX therapy on peripheral Th17 cells and IL-17/IL-6 secretion in RA patients. Twenty active RA patients were treated with oral MTX 15 mg per week (MTX group, n = 10), or hypodermal adalimumab 40 or 80 mg every other week (ADA group, n = 10). Peripheral blood samples were taken for laboratory evaluation at week 0 and week 12 of treatment, including flowcytometric detection of peripheral CD4(+) IL-17(+) cells, RT-PCR detection of mRNA expressions of IL-17, RORc and FoxP3, and ELISA determination of serum IL-17 and IL-6. Ten age and sex marched healthy volunteers were included as normal controls. Results showed that (1) DAS28 in both groups improved at week 12 compared to week 0 (3.9 ± 1.3 vs. 6.4 ± 1.4 and 3.2 ± 0.9 vs. 5.2 ± 0.9, respectively). (2) The percentage and MFI of peripheral CD4(+) IL-17(+) cells in RA patients were significantly higher comparing to normal controls (1.64 ± 0.97% vs. 0.75 ± 0.20%, p < 0.01; and 29.8 ± 9.7 vs. 19.8 ± 4.6, p < 0.05, respectively), and positively correlated with ESR and DAS28. Peripheral Th17 cells and serum IL-6 in RA patients decreased after treatment (from 1.60 ± 0.78% to 1.28 ± 0.41%, and from 17.15 ± 14.53 pg/ml to 6.97 ± 5.51 pg/ml, p < 0.05, respectively). Peripheral FoxP3 mRNA expression in active RA patients was significantly lower comparing to normal controls, and negatively correlated with ESR. Baseline Th17 percentage of RA patients negatively correlated with DAS28 improvement after treatment. In conclusion, adalimumab and MTX treatment down regulates peripheral Th17 cells and serum IL-6 level in RA patients. Baseline Th17 level negatively predicts the effect of adalimumb/MTX treatment.
评估阿达木单抗和甲氨蝶呤（MTX）治疗对 RA 患者外周血 Th17 细胞和 IL-17/IL-6 分泌的影响。
20 例活动期 RA 患者分别接受口服 MTX（每周 15mg，MTX 组，n=10）或皮下注射阿达木单抗（每隔一周 40 或 80mg，ADA 组，n=10）治疗。在治疗的第 0 周和第 12 周采集外周血进行实验室评估，包括流式细胞术检测外周血 CD4+IL-17+细胞、RT-PCR 检测 IL-17、RORc 和 FoxP3mRNA 表达、ELISA 检测血清 IL-17 和 IL-6。纳入 10 名年龄和性别匹配的健康志愿者作为正常对照。
（1）与治疗前相比，两组 DAS28 在第 12 周时均有所改善（3.9±1.3 比 6.4±1.4 和 3.2±0.9 比 5.2±0.9）。（2）与正常对照组相比，RA 患者外周血 CD4+IL-17+细胞的百分比和 MFI 明显更高（1.64±0.97%比 0.75±0.20%，p<0.01；29.8±9.7 比 19.8±4.6，p<0.05），且与 ESR 和 DAS28 呈正相关。治疗后，RA 患者外周血 Th17 细胞和血清 IL-6 下降（从 1.60±0.78%降至 1.28±0.41%和从 17.15±14.53pg/ml 降至 6.97±5.51pg/ml，p<0.05）。与正常对照组相比，活动期 RA 患者外周血 FoxP3mRNA 表达明显降低，且与 ESR 呈负相关。RA 患者治疗前 Th17 百分比与治疗后 DAS28 改善呈负相关。
阿达木单抗和 MTX 治疗可下调 RA 患者外周血 Th17 细胞和血清 IL-6 水平。治疗前 Th17 水平与阿达木单抗/MTX 治疗效果呈负相关。
