Cysteine-rich 61 (Cyr61): a biomarker reflecting disease activity in rheumatoid arthritis
Cysteine-rich 61 (Cyr61): a biomarker reflecting disease activity in rheumatoid arthritis
复制标题
富含半胱氨酸 61 (Cyr61)：反映类风湿关节炎疾病活动性的生物标志物
DOI：
10.1186/s13075-019-1906-y
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发表时间：
2019-05-21
影响因子：
4.9
通讯作者：
Zhang, Zhuoli
中科院分区：
文献类型：
--
作者：
Fan, Yong;Yang, Xinlei;Zhang, Zhuoli
大量临床前研究表明，富含半胱氨酸的61(Cyr61)在类风湿关节炎(RA)的发病机制中起着重要作用。但很少有文献讨论循环Cyr61在RA患者中的临床价值。本研究旨在探讨类风湿关节炎(RA)患者血清Cyr61水平及其与疾病活动性的关系。在登记时采集血清样本。为了进一步证实这一发现，根据一项注册的临床试验建立了一个独立的验证队列。分别在基线和统一治疗后12 采集活动期RA患者的配对血清样本。采用双抗体夹心酶联免疫吸附试验检测血清Cyr61浓度。结果177例确诊类风湿关节炎患者和50例年龄、性别匹配的健康对照进入训练队列。RA患者血清Cyr61浓度显著升高，显示出良好的鉴别诊断能力(曲线下面积(AUC) = 为0.98，P<； 为0.001)。此外，活动期RA患者血清Cyr61水平显著低于缓解期/低活动期患者，且与疾病活动度综合评分及统计学上几乎所有成分呈负相关。进一步的验证队列研究(n= 77)显示，在12 周，ACR应答者的Cyr61水平显著升高(ACR20/50/70)，而无应答者的Cyr61水平与基线相比无显著变化。结论RA患者血清Cyr61水平显著高于健康对照组。Cyr61浓度与RA疾病活动性呈负相关，并在这些治疗应答者中上调。试验登记联合疗法预防RA复发，NCT02320630。注册于2014年12月19日，
BackgroundNumerous preclinical studies have revealed a critical role of cysteine-rich 61 (Cyr61) in the pathogenesis of rheumatoid arthritis (RA). But there is little literature discussing the clinical value of circulation Cyr61 in RA patients. The aim of our study is to investigate the serum Cyr61 level and its association with disease activity in RA patients.MethodsA training cohort was derived from consecutive RA patients who visited our clinic from Jun 2014 to Nov 2018. Serum samples were obtained at the enrollment time. To further confirm discovery, an independent validation cohort was set up based on a registered clinical trial. Paired serum samples of active RA patients were respectively collected at baseline and 12 weeks after uniformed treatment. Serum Cyr61 concentration was detected by enzyme-linked immunosorbent assay. The comparison of Cyr61 between RA patients and controls, the correlation between Cyr61 levels with disease activity, and the change of Cyr61 after treatment were analyzed by appropriate statistical analyses.ResultsA total of 177 definite RA patients and 50 age- and gender-matched healthy controls were enrolled in the training cohort. Significantly elevated serum Cyr61 concentration was found in RA patients, demonstrating excellent diagnostic ability to discriminate RA from healthy controls (area under the curve (AUC) = 0.98,P< 0.001). In addition, the Cyr61 level in active RA patients was significantly lower than that in patients in remission/low disease activity, and it was inversely correlated with composite disease activity scores and almost all of the components in statistic. Further study in the validation cohort (n= 77) showed a significant increase of the Cyr61 level at 12 weeks in ACR responders (ACR20/50/70), while no significant change of the Cyr61 level from baseline was observed in non-responders.ConclusionsSerum Cyr61 levels were remarkably increased in RA patients compared with those in healthy controls. The Cyr61 concentration was inversely correlated with RA disease activity and upregulated in those therapeutic responders.Trial registrationCombination Therapy Prevents the Relapse of RA, NCT02320630 . Registered 19 December 2014,