title: Abnormal high-expression of CD154 on T lymphocytes of ankylosing spondylitis patients is down-regulated by etanercept treatment.
abstract: 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.
authors.affiliation: Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-Sen University, 510630 Guangzhou, China.
authors.forename: Qu
authors.initials: Q
authors.lastname: Lin
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Lin
authors.forename: Jieruo
authors.initials: J
authors.lastname: Gu
authors.forename: Feng
authors.initials: F
authors.lastname: Huang
authors.forename: Tianwang
authors.initials: T
authors.lastname: Li
authors.forename: Qiujing
authors.initials: Q
authors.lastname: Wei
authors.forename: Zetao
authors.initials: Z
authors.lastname: Liao
authors.forename: Shuangyan
authors.initials: S
authors.lastname: Cao
authors.forename: Yingjuan
authors.initials: Y
authors.lastname: Jiang
authors.forename: Jinxian
authors.initials: J
authors.lastname: Huang
mesh_terms: D000293:Adolescent; D000328:Adult; D018501:Antirheumatic Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D023201:CD40 Ligand / Q000187:drug effects* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D018124:Receptors, Tumor Necrosis Factor; D013167:Spondylitis, Ankylosing / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; D007074:Immunoglobulin G; D010919:Placebos; D018124:Receptors, Tumor Necrosis Factor; D023201:CD40 Ligand; D000068800:Etanercept