Relationship of serum TWEAK level to cytokine level, disease activity, and response to anti-TNF treatment in patients with rheumatoid arthritis

Objectives: To determine the serum concentration of tumour necrosis factor (TNF)-related weak inducer of apoptosis (TWEAK) in patients with rheumatoid arthritis RA) and to investigate the relationship between TWEAK level and disease activity, proinflammatory cytokine levels, and response to anti-TNF treatment. Methods: Serum samples from 40 patients with RA, 40 patients with ankylosing spondylitis (AS), and 40 healthy subjects were collected. Serum samples from 26 patients with RA who received etanercept treatment were also collected in the 12th week of etanercept therapy. Serum TWEAK, TNF alpha, and interleukin (IL)-6 levels were determined by enzyme-linked immunosorbent assay (ELISA), and disease activity of RA was assessed according to the 28-joint count Disease Activity Score (DAS28). Results: Patients with RA had significantly higher serum levels of TWEAK, TNF alpha, and IL-6 compared with controls (p < 0.05). Patients with AS also had significantly higher serum levels of TNFa and IL-6 (p < 0.05), but their serum TWEAK levels were not different from those of the controls. In patients with RA, serum TWEAK levels correlated with DAS28 (r(2) =0.452, p=0.012) and TNF alpha levels (r(2) =0.653, p<0.001) but not with IL-6 levels. Among RA patients who were treated with etanercept, responders showed a significant decrease in serum TWEAK levels at the 12th week of treatment, whereas TWEAK levels in nonresponders were not different from their baseline levels. Conclusions: Serum levels of TWEAK were significantly elevated in patients with RA, and reflected disease activity and short-term response to etanercept treatment.