Identification of 7 Proteins in Sera of RA Patients with Potential to Predict ETA/MTX Treatment Response.
Identification of 7 Proteins in Sera of RA Patients with Potential to Predict ETA/MTX Treatment Response.
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DOI：
10.7150/thno.12403
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发表时间：
2015
期刊：
影响因子：
12.4
通讯作者：
Cosette P
中科院分区：
文献类型：
--
作者：
Obry A;Hardouin J;Lequerré T;Jarnier F;Boyer O;Fardellone P;Philippe P;Marcelli C;Loët XL;Vittecoq O;Cosette P
目的：近年来创新生物制剂的发展为患者管理开辟了迷人的途径。在类风湿性关节炎中，目前有许多生物制剂可用，其选择主要是凭经验确定的。重要的是，给定的生物制剂可能在一小部分患者中没有活性，甚至可能引起副作用。在这里，我们进行了一项比较蛋白质组学研究，试图确定一个预测性的治疗诊断标志的无反应的类风湿关节炎患者接受依那西普/甲氨蝶呤组合。方法：在治疗暴露前从22例活动性RA患者队列中收集血清样本。然后设计了一种蛋白质组学“无标记”方法，使用质谱法定量蛋白质生物标志物。为了验证这些结果，对第二组进行感兴趣的蛋白候选物的相对定量，然后进行绝对定量。判断标准是治疗6个月时根据EULAR标准评估的依那西普/甲氨蝶呤联合治疗的反应。结果：这些研究导致了一组12个生物标志物的鉴定，这些生物标志物具有预测治疗反应的能力。靶向定量分析允许确认来自后一种组合的7种蛋白质在16名患者的新队列中的潜力。通过ELISA对第二组进一步评估两种高度区分的蛋白质，PROS和CO 7。通过将每种蛋白质的浓度阈值与正确的分类（应答者vs无应答者）相结合，灵敏度和特异性分别达到88.9%和100%。结论：在甲氨蝶呤/依那西普治疗前，几种血清蛋白的丰度，特别是PROS和CO 7，与RA患者治疗开始后6个月的反应状态相关。
Objective: The recent growth of innovating biologics has opened fascinating avenues for the management of patients. In rheumatoid arthritis, many biologics are currently available, the choice of which being mostly determined empirically. Importantly, a given biologic may not be active in a fraction of patients and may even provoke side effects. Here, we conducted a comparative proteomics study in attempt to identify a predictive theranostic signature of non-response in patients with rheumatoid arthritis treated by etanercept/methotrexate combination. Methods: A serum sample was collected prior to treatment exposure from a cohort of 22 patients with active RA. A proteomic “label free” approach was then designed to quantitate protein biomarkers using mass spectrometry. To verify these results, a relative quantification followed by an absolute quantification of interesting protein candidates were performed on a second cohort. The criterion of judgment was the response to etanercept/methotrexate combination according to the EULAR criteria assessed at 6 months of treatment. Results: These investigations led to the identification of a set of 12 biomarkers with capacity to predict treatment response. A targeted quantitative analysis allowed to confirm the potential of 7 proteins from the latter combination on a new cohort of 16 patients. Two highly discriminating proteins, PROS and CO7, were further evaluated by ELISA on this second cohort. By combining the concentration threshold of each protein associated to a right classification (responders vs non-responders), the sensitivity and specificity reached 88.9 % and 100 %, respectively. Conclusion: Prior to methotrexate/etanercept treatment, abundance of several sera proteins, notably PROS and CO7, were associated to response status of RA patients 6 month after treatment initiation.