Reduction of Serum ADAM17 Level Accompanied with Decreased Cytokines after Abatacept Therapy in Patients with Rheumatoid Arthritis

Abstract

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.