强直性脊柱炎患者外周血T淋巴细胞亚群和T淋巴细胞上CD154表达的变化和意义

Changes of T lymphocyte subsets and expression of costimulatory molecule CD154 on T-cells in peripheral blood from patients with ankylosing spondylitis

目的探讨强直性脊柱炎（AS）患者外周血T淋巴细胞亚群分布和T淋巴细胞上共刺激分子CD154的表达及依那西普治疗对其的影响。方法用流式细胞仪检测66例AS患者（其中活动期39例，非活动期27例；按临床特征分为外周关节和中轴均受累者35例和单独中轴受累31例）、30例类风湿关节炎（RA）患者及30名健康志愿者外周血T淋巴细胞亚群分布和CD154在CD3＋T淋巴细胞上的表达。此外，观察39例AS活动期患者在随机双盲依那西普和安慰剂对照试验中，用药前后CD154的变化。结果①AS和RA患者CD4^＋T淋巴细胞均较健康志愿者高（P〈0．05），而CD8＋T淋巴细胞较健康志愿者低（P〈0．05）；AS患者外周血T细胞上CD154的表达较健康志愿者和RA患者都明显升高（P〈0.05）；②活动期或外周关节受累AS患者T细胞CD154的表达分别较稳定期或单独中轴受累AS患者明显升高（P〈0．05）；且CD154的表达与关节压痛数、关节肿胀数呈正相关（P＜0．05）；③在依那西普试验的第6周，依那西普组AS患者（19例）T淋巴细胞CD154表达较安慰剂组（20例）明显下降（P〈0．05），与健康志愿者差异无统计学意义（P〉0．05）。结论AS患者外周血存在T淋巴细胞亚群紊乱和T淋巴细胞上共刺激分子CD154异常表达，可作为临床评价AS病情活动性和依那西普疗效的生物指标之一。

Objective To study T lymphocyte subsets and expression of costimulatory molecule CD154 on T-cells in peripheral blood from patients with ankylosing spondylitis and their changes after treated with Enbrel. Methods Sixty-six patients with AS （39 active and 27 inactive, 35 axial and peripheral joint involvement and 31 axial involvement only）, 30 patients with rheumatoid arthritis （RA）, 30 healthy volunteers were analyzed. The expression of CD154 on CD3^＋ T cell as well as T-cells subsets were evaluated using flow cytometry respectively. The changes of the expression of costimulatory molecule CD154 in 39 active AS patients （Enbrel treatment or placebo treatment） were observed in a randomized, double-blind, placebocontrolled trial. Results ①Frequency of CD3^＋CD4^＋ T cell in AS and RA patients were significantly higher than that of healthy volunteers, and CD154 expression on CD3^＋ T cells in peripheral blood in AS patients was all significantly higher than that in healthy volunteers and RA patients （P〈0.05）. ② The expression of CD154 on CD3^＋ T cells in the peripheral blood of active AS or AS patients with peripheral joint involvement were significantly higher than those in inactive or axial involvement only AS patients （P〈0.05）, and CD154 on CD3^＋ T cells was positively correlated with tender joint count and swollen joint count （P〈0.05） . ③ Compared with placebo, in AS patients group, there was significant reduction in CD154 expression on CD3^＋ T cells in Enbrel group at week 6 （P〈0.05）, there was no significant difference between Enbrel group and healthy volunteers at week 6 （P〉0.05）. Conclusion T lymphocyte subsets are significantly abnormal and CD154 is overexpressed on T-cells in peripheral blood of patients with AS. A six-week course of treatment with Enbrel in active AS can induce a down-regulation of the expression of CD154 on T cells.