Umemura Masayu, Isozaki Takeo, Ishii Syo, Seki Shinya, Oguro Nao, Miura Yoko, Miwa Yusuke, Nakamura Masanori, Inagaki Katsunori, Kasama Tsuyoshi
Division of Rheumatology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan;
Department of Orthopedics, Showa University Northern Yokohama Hospital, Yokohama, Japan;
Int J Biomed Sci. 2014 Dec;10(4):229-35.
A disintegrin and metalloprotease 17 (ADAM17) appears to be recognized as an important player in tissue destruction and also exacerbation of inflammation related with increased activities of angiogenesis in several pathological conditions. To examine the modulation of serum levels of ADAM17 and inflammatory cytokines in patients with rheumatoid arthritis (RA) in response to therapy of abatacept (ABT). Twenty four patients with RA were enrolled in our study. Serum was collected immediately prior to (baseline) and 24 weeks after starting ABT therapy. Serum levels of ADAM17 and cytokines/chemokine were quantified using enzyme-linked immunosorbent assay. ADAM17 level was markedly higher in RA patients than in healthy individuals. Positive correlation was observed between the baseline ADAM17 and CX3CL1 at baseline. There was a significant overall reduction of RA disease activity (Disease Activity Score 28) from 4.73 to 2.79 after 24 weeks after the ABT therapy. Furthermore, there was a significant reduction in serum level of ADAM17 in RA patients, and the patients achieved clinical responses, and also clinical remission had a significant decrease in ADAM17 level and also levels of tumor necrosis factor α, IL-6 and CX3CL1 after 24 weeks of ABT therapy. Our results suggest that the suppression of ADAM17 secretion and function seems to be a crucial therapeutic target in the treatment of ABT in patients with RA.
解整合素金属蛋白酶17（ADAM17）似乎被认为是组织破坏以及在几种病理状况下与血管生成活性增加相关的炎症加剧过程中的一个重要因素。为了研究类风湿关节炎（RA）患者血清中ADAM17水平和炎性细胞因子在接受阿巴西普（ABT）治疗后的变化情况。24例RA患者纳入我们的研究。在开始ABT治疗前（基线）和治疗24周后立即采集血清。使用酶联免疫吸附测定法定量血清中ADAM17和细胞因子/趋化因子的水平。RA患者的ADAM17水平明显高于健康个体。在基线时观察到ADAM17与CX3CL1之间存在正相关。ABT治疗24周后，RA疾病活动度（疾病活动评分28）从4.73显著降至2.79。此外，RA患者血清中ADAM17水平显著降低，患者获得临床反应，并且在ABT治疗24周后，临床缓解患者的ADAM17水平以及肿瘤坏死因子α、IL-6和CX3CL1水平也显著下降。我们的结果表明，抑制ADAM17分泌和功能似乎是RA患者ABT治疗中的一个关键治疗靶点。
