Zabludowitz Center for Autoimmune Diseases, Sheba Medical Center, Ramat Gan, Israel; Department of Internal Medicine 'B', Sheba Medical Center, Ramat Gan, Israel; Rheumatology Unit, Sheba Medical Center, Ramat Gan, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Zabludowitz Center for Autoimmune Diseases, Sheba Medical Center, Ramat Gan, Israel.
Pharmacol Res. 2019 Mar;141:623-626. doi: 10.1016/j.phrs.2018.11.009. Epub 2018 Nov 8.
14-3-3η protein is a proinflammatory mediator that may represent a novel diagnostic and prognostic biomarker for rheumatoid arthritis (RA). We assessed the correlation between changes in serum 14-3-3η levels and changes in clinical disease activity measures in RA patients treated with Tofacitinib (TOF). Paired serum samples from 35 patients with RA were obtained at baseline and 5 months after the initiation of treatment with TOF. The levels of 14-3-3η were measured by JOINT stat 14-3-3η ELISA test kits (Augurex Life Sciences Corp.). The cut-off was defined as 0.19 ng/ml. 14-3-3η positivity was found in 57% of the patients at baseline and in 37% of the patients after 5 months of treatment. Mean ± SD baseline 14-3-3η levels [4.92 ± 8.86 ng/ml] were significantly higher (p < 0.005) than 14-3-3η levels following treatment [1.97 ± 4.59 ng/ml]. A statistically significant improvement (p < 0.001) of CDAI, SDAI, DAS4ESR and DAS4CRP was achieved after 5 month of treatment. Decrease in 14-3-3η protein levels was highly correlated with improvement in DAS4ESR (r = 0.50, p < 0.01), DAS4CRP (r = 0.46, p < 0.01) and ESR (r = 0.36, p = 0.03) and moderately correlated with improvement in CDAI (r = 0.32, p = 0.065) and SDAI (r = 0.33, p = 0.051). The correlation between decrease in 14-3-3η levels and improvement in DAS4ESR remained significant in a partial correlation analysis controlling for ESR (r = 0.39, p = 0.02). This study demonstrates that in RA patients who were treated with TOF, decrease in 14-3-3η levels is correlated with improvement in clinical disease activity parameters. The 14-3-3η protein may serve as an objective biomarker for monitoring of TOF therapy response.
14-3-3η 蛋白是一种促炎介质，可能代表类风湿关节炎 (RA) 的新型诊断和预后生物标志物。我们评估了接受托法替尼 (TOF) 治疗的 RA 患者血清 14-3-3η 水平变化与临床疾病活动测量变化之间的相关性。在开始 TOF 治疗前和治疗 5 个月后，从 35 名 RA 患者中获得配对的血清样本。通过 JOINT stat 14-3-3η ELISA 试剂盒 (Augurex Life Sciences Corp.) 测量 14-3-3η 水平。将截定点定义为 0.19ng/ml。基线时 57%的患者 14-3-3η 阳性，治疗 5 个月后 37%的患者 14-3-3η 阳性。平均 ± SD 基线 14-3-3η 水平 [4.92 ± 8.86ng/ml] 显著高于治疗后 [1.97 ± 4.59ng/ml] (p<0.005)。治疗 5 个月后，CDAI、SDAI、DAS4ESR 和 DAS4CRP 均达到统计学显著改善 (p<0.001)。14-3-3η 蛋白水平下降与 DAS4ESR(r=0.50，p<0.01)、DAS4CRP(r=0.46，p<0.01)和 ESR(r=0.36，p=0.03)的改善高度相关，与 CDAI(r=0.32，p=0.065)和 SDAI(r=0.33，p=0.051)的改善中度相关。在控制 ESR 的偏相关分析中，14-3-3η 水平下降与 DAS4ESR 改善之间的相关性仍然显著(r=0.39，p=0.02)。本研究表明，在接受 TOF 治疗的 RA 患者中，14-3-3η 水平下降与临床疾病活动参数的改善相关。14-3-3η 蛋白可能是监测 TOF 治疗反应的客观生物标志物。
