肿瘤坏死因子-α拮抗剂对类风湿关节炎和强直性脊柱炎患者血清白细胞介素-17和外周血 Th17细胞比例的影响  

Elevated serum interleukin-17 level but not Th17 cell percentage reduced in patients with rheumatoid arthritis and ankylosing spondylitis after 40 weeks tumor necrosis factor-α blockade therapy

作　　者：林丽[1] 叶玲英[1] 殷健[1] 张立斌[1] 徐沪济[1] 

机构地区：[1]第二军医大学附属长征医院风湿免疫科,上海200003

出　　处：《中华风湿病学杂志》2014年第10期661-664,I0001,共5页Chinese Journal of Rheumatology

基　　金：国家自然科学基金（81010125,81273283）

摘　　要：目的初步探讨外周血 Th17细胞亚群的比例以及 IL-17的表达水平在 RA 和 AS 患者接受 TNF-α拮抗剂治疗前后的改变及其意义。方法选择 RA 患者27例和 AS 患者22例，2种疾病中各有14例患者接受 TNF-α拮抗剂治疗40周。对照组24名来源于健康献血者。采用流式细胞术检测外周血 CD4＋T 细胞中 Th17细胞亚群的比例，ELISA 检测外周血 IL-17表达水平。符合正态分布数据采用2个独立样本 t 检验，不符合正态分布则采用 Wilcoxon 秩和检验，患者治疗前后的比较采用配对 t 检验。结果治疗前，RA 和 AS 患者外周血 CD4＋ T 细胞中 Th17细胞亚群的比例显著高于健康对照组[RA 1.03%（0.66%，1.78%）与健康对照0.50%（0.43%，0.67%），Z=-3.236，P＆lt;0.01；AS（1.16±0.09）%与健康对照（0.59±0.06）%，t=5.226，P〈0.01]。同样，IL-17的表达水平在2组疾病中也显著升高[RA（32.3±2.5） pg/ml，健康对照（14.3±2.5） pg/ml，t=5.070，P＆lt;0.01；AS 28.98（23.84，36.14） pg/ml，健康对照11.84（5.33，22.12） pg/ml，Z=-4.103，P〈0.01]。 TNF-α拮抗剂治疗后，2组疾病 CD4＋T 细胞中 Th17细胞亚群比例无明显变化[RA 驻（0.1045±0.2126）%；AS 驻（0.0025±0.1838）%]，但 IL-17表达水平则明显下降[RA 驻（-13.5±5.0） pg/ml；AS 驻（-16.0±1.9） pg/ml]。结论 Th17细胞及其分泌的细胞因子 IL-17在 RA 和 AS 的发病机制中起重要作用，TNF-α拮抗剂对 AS 和 RA 患者 Th17细胞亚群炎症细胞因子的分泌功能有明显的抑制作用，但40周的治疗仍不能降低 Th17细胞比例，这可能是 TNF-α拮抗剂短期治疗后疾病复发的原因之一。Objective To explore the effect of tumor necrosis factor-alpha（TNF-α） blockade therapy on circulating Th17 cell percentage and serum interleukin （IL）-17 level in patients with rheumatoid arthritis （RA） and ankylosing spondylitis （AS）. Methods Twenty-seven RA and 22 AS patients were recruited, of which 14 cases from both diseases received 40 weeks TNF blockade therapy. Twenty-four healthy blood donors were used as controls. The frequencies of circulating Th17 cells were determined by flowcytometry, and serum IL-17 level were measured by enzyme linked immunosorbent assay（ELISA）. Results Significantly higher baseline circulating Th17 cells were observed in active RA and AS patients compared with the healthy controls[RA 1.03%（0.66%,1.78%） vs controls 0.50%（0.43%,0.67%）, Z=-3.236, P〈0.01; AS（1.16±0.09）%vs controls （0.59 ±0.061）% , t =5.226, P 〈0.01]. Similarly, serum IL-17 level were significantly elevated in patients with both diseases compared with controls[RA（32.3±2.5） pg/ml vs controls（14.3±2.5） pg/ml, t=5.070, P〈0.01; AS 28.98（23.84,36.14） pg/ml vs controls 11.84（5.33,22.12） pg/ml, Z=-4.103, P＆lt;0.01]. After TNF-α blockade therapy, serum IL-17 was significantly decreased in both diseases groups[RA △（-13.5± 5.0） pg/ml and AS △（-16.0±1.9） pg/ml]. In contrast, no significant differences were found in the frequencies of circulating Th17 cells[RA △（0.104 5±0.212 6）% and AS △（0.002 5±0.183 8）%]. Conclusion Th17 cells and IL-17 have been implicated in the pathogenesis of RA and AS. TNF-α blockade can partially inhibit the function of Th17 cells. However, it is unable to reduce the frequencies of these cells in the circulation after 40 weeks therapy, which may explain the reasons for the relapse.

关 键 词：TH17 细胞 白细胞介素 17 肿瘤坏死因子 α 关节炎  类风湿 脊柱炎  强直性 

分 类 号：R346[医药卫生—基础医学]