Shi Rui, Chen Muzhi, Litifu Bahaerguli
a Department of Rheumatology and Immunology , Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine , Xinjiang , China.
Mod Rheumatol. 2018 Jan;28(1):126-132. doi: 10.1080/14397595.2017.1317384. Epub 2017 Jun 28.
To investigate the correlation of nine potential biomarkers with clinical response to etanercept (ETN) therapy in establish rheumatoid arthritis (RA) patients.
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.
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).
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.
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。
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。
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)。
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。