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血清白细胞介素-6和生存素水平可预测确诊类风湿关节炎患者对依那西普治疗的临床反应。

Serum interleukin-6 and survivin levels predict clinical response to etanercept treatment in patients with established rheumatoid arthritis.

作者信息

Shi Rui, Chen Muzhi, Litifu Bahaerguli

机构信息

a Department of Rheumatology and Immunology , Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine , Xinjiang , China.

出版信息

Mod Rheumatol. 2018 Jan;28(1):126-132. doi: 10.1080/14397595.2017.1317384. Epub 2017 Jun 28.

Abstract

OBJECTIVES

To investigate the correlation of nine potential biomarkers with clinical response to etanercept (ETN) therapy in establish rheumatoid arthritis (RA) patients.

METHODS

Seventy-three patients with established RA were enrolled in the prospective cohort study. Sixty-nine of 73 cases were included into final analysis for response after 24-week ETN therapy. Serum expression of nine studied proteins was measured by enzyme-linked immunosorbent assay (ELISA). Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-17A, IL-21, IL-34, RANKL, survivin, and COMP were selected as candidate biomarkers.

RESULTS

Serum IL-6 level was increased in responders than in nonresponders at baseline, p = .034; to the contrary, serum survivin level was decreased in responders, p = .009. Receiver operating characteristic (ROC) curve illuminated the combination of IL-6 and survivin expressions could predict clinical response with a high AUC 0.875, 95% CI: 0.771-0.976. Furthermore, we found the combination of IL-6 high expression and survivin low expression increased the responding possibility to nearly 20-fold (OR 19.687, 95% CI: 4.087-94.839, p < .001) compared to IL-6 low or survivin high expression by univariate analysis. However, only survivin low expression (p = .002) and CRP (p = .014) high expression were independent predictive factors for achieving clinical response, while IL-6 lack independent predictive value (p = .267).

CONCLUSIONS

Comprehensive measurement of IL-6 and survivin in serum could be served as a convincing biomarker for clinical response in ETN-treated patients with established RA.

摘要

目的

探讨9种潜在生物标志物与确诊类风湿关节炎(RA)患者对依那西普(ETN)治疗临床反应的相关性。

方法

73例确诊RA患者纳入前瞻性队列研究。73例中的69例在接受24周ETN治疗后纳入最终反应分析。采用酶联免疫吸附测定(ELISA)检测9种研究蛋白的血清表达。选择肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、IL-6、IL-17A、IL-21、IL-34、RANKL、生存素和软骨寡聚基质蛋白(COMP)作为候选生物标志物。

结果

基线时,反应者血清IL-6水平高于无反应者,p = 0.034;相反,反应者血清生存素水平降低,p = 0.009。受试者工作特征(ROC)曲线表明,IL-6和生存素表达的联合可预测临床反应,曲线下面积(AUC)为0.875,95%可信区间(CI):0.771 - 0.976。此外,单因素分析发现,与IL-6低表达或生存素高表达相比,IL-6高表达和生存素低表达的联合使反应可能性增加近20倍(比值比[OR] 19.687,95% CI:4.087 - 94.839,p < 0.001)。然而,只有生存素低表达(p = 0.002)和C反应蛋白(CRP)高表达(p = 0.014)是实现临床反应的独立预测因素,而IL-6缺乏独立预测价值(p = 0.267)。

结论

综合检测血清中的IL-6和生存素可作为确诊RA患者接受ETN治疗临床反应的可靠生物标志物。

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