Abnormal high-expression of CD154 on T lymphocytes of ankylosing spondylitis patients is down-regulated by etanercept treatment.

The pathogenesis of ankylosing spondylitis (AS) still remains an enigma. Although some studies have indicated the importance of T-cells and proinflammatory cytokines in the pathogenesis of the AS, it is still unknown whether co-stimulatory molecule CD154 participates in the pathogenesis of AS and how its level changes during the anti-TNF-alpha treatment of AS. This study is performed to evaluate the expression of CD154 in peripheral blood T-lymphocytes of patients with AS and observe the change of CD154 in etanercept-treated AS patient. We collected the peripheral blood and clinical data from 66 AS, 30 rheumatoid arthritis (RA) patients, and 30 healthy controls. Thirty-nine active AS patients were enrolled in a randomized double-blind placebo-controlled trial. We followed up 37 cases that fulfilled the ASAS20 response criteria after they finished etanercept treatment till week 48. The percentage of CD3+CD154+ in peripheral blood lymphocytes was evaluated by flow cytometry. We found that CD154 expression in AS patients was significantly higher than that in healthy volunteers and RA patients (both P < 0.001). The expressions of CD154 in AS patients at active stage or with peripheral joint involvement were significantly higher than those at stable stage or with axial involvement alone (P = 0.005 and 0.044, respectively). The expression of CD154 decreased in AS patients treated with etanercept compared with patients treated with placebo at week 6 (P < 0.001). Compared with healthy volunteers, the expression of CD154 in 16 AS patients who relapsed after finishing etanercept treatment was elevated again (P = 0.012). These findings show that co-stimulatory molecule CD154 is overexpressed on T-lymphocytes in peripheral blood of AS patients and can be down-regulated by etanercept treatment, which suggest that CD154 might be involved in the inflammatory evolvement of AS and might be a potential biomarker to monitor AS disease activity and the effect of etanercept treatment.