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类风湿关节炎中抗肿瘤坏死因子-α反应与血清可溶性CD30水平升高有关。

Anti-tumor necrosis factor-alpha response in rheumatoid arthritis is associated with an increase in serum soluble CD30.

作者信息

Gerli Roberto, Lunardi Claudio, Bocci Elena Bartoloni, Bobbio-Pallavicini Francesca, Schillaci Giuseppe, Caporali Roberto, Bistoni Onelia, Pirro Matteo, Pitzalis Costantino, Montecucco Carlomaurizio

机构信息

Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy.

出版信息

J Rheumatol. 2008 Jan;35(1):14-9. Epub 2007 Dec 1.

PMID:18061981
Abstract

OBJECTIVE

Patients with rheumatoid arthritis (RA) display high serum concentrations of soluble CD30 (sCD30), which correlate with counter-regulatory activity of CD30+ T cells in the inflamed joint. To verify the contribution of this T cell subset to disease remission, sCD30 levels were analyzed longitudinally in patients with active RA following infliximab therapy.

METHODS

Infliximab plus methotrexate were started in 39 patients with active RA, while 20 patients with inactive disease, controlled by stable doses of methotrexate, acted as controls. Serial evaluations of sCD30 concentrations and disease activity indexes were performed throughout 38 weeks.

RESULTS

sCD30 levels were higher in patients than in healthy controls. Rapid infliximab-induced decrease in disease activity was associated with an overall increase of sCD30 levels. In contrast, levels remained stable in controls. An inverse correlation between sCD30 levels and Disease Activity Score 28 was observed from the 22nd week of infliximab treatment. Analysis of sCD30 levels according to American College of Rheumatology response showed, after an initial general enhancement of sCD30 concentrations, a persistent increase of sCD30 in responders, but not in nonresponders.

CONCLUSION

sCD30 serum levels are enhanced by tumor necrosis factor-a (TNF-a) blockade in patients with active RA and inversely correlated with disease activity, but only after some weeks of treatment. Of interest, a sustained increase of sCD30 is present only in subjects with evidence of persistent clinical response to anti-TNF-alpha. As sCD30 serum levels mirror antiinflammatory activity of joint T cells, the present data may suggest a role of synovial counter-regulatory CD30+ T cells in the induction of infliximab-mediated remission in RA.

摘要

目的

类风湿关节炎(RA)患者血清中可溶性CD30(sCD30)浓度较高,这与炎症关节中CD30+T细胞的负调节活性相关。为验证该T细胞亚群对疾病缓解的作用,对英夫利昔单抗治疗后的活动性RA患者进行了sCD30水平的纵向分析。

方法

39例活动性RA患者开始使用英夫利昔单抗加甲氨蝶呤治疗,20例病情稳定、由甲氨蝶呤稳定剂量控制的非活动性疾病患者作为对照。在38周内对sCD30浓度和疾病活动指数进行了系列评估。

结果

患者的sCD30水平高于健康对照。英夫利昔单抗快速诱导的疾病活动度降低与sCD30水平的总体升高相关。相比之下,对照组的水平保持稳定。从英夫利昔单抗治疗第22周起,观察到sCD30水平与疾病活动评分28呈负相关。根据美国风湿病学会的反应分析sCD30水平显示,在sCD30浓度最初普遍升高后,反应者的sCD30持续升高,而非反应者则不然。

结论

活动性RA患者中,肿瘤坏死因子-α(TNF-α)阻断可提高sCD30血清水平,且与疾病活动度呈负相关,但仅在治疗数周后出现。有趣的是,只有在对抗TNF-α有持续临床反应的受试者中,sCD30才会持续升高。由于sCD30血清水平反映了关节T细胞的抗炎活性,目前的数据可能提示滑膜负调节性CD30+T细胞在RA中诱导英夫利昔单抗介导的缓解中发挥作用。

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