Department of Basic Medical Sciences, Laboratory of Biology, School of Medicine, University of Athens, Greece; Laboratory of Cell and Gene Therapy Foundation for Biomedical Research of the Academy of Athens (IIBEAA), Greece.
J Crohns Colitis. 2013 Nov;7(10):e461-70. doi: 10.1016/j.crohns.2013.02.021. Epub 2013 Apr 3.
The infliximab (IFX) has dramatically improved the treatment of Crohn's disease (CD). However, the need for predictive factors, indicative of patients' response to IFX, has yet to be met. In the current study, proteomics technologies were employed in order to monitor for differences in protein expression in a cohort of patients following IFX administration, aiming at identifying a panel of candidate protein biomarkers of CD, symptomatic of response to treatment. We enrolled 18 patients, who either had achieved clinical and serological remission (Rm, n=6), or response (Rs, n=6) and/or were PNRs (n=6), to IFX. Serum samples were subjected to two-dimensional Gel Electrophoresis. Following evaluation of densitometrical data, protein spots exhibiting differential expression among the groups, were further characterized by MALDI-TOF-MS. Identified proteins where evaluated by immunoblot analysis while functional network association was carried out to asses significance. Proteins apolipoprotein A-I (APOA1), apolipoprotein E (APOE), complement C4-B (CO4B), plasminogen (PLMN), serotransferrin (TRFE), beta-2-glycoprotein 1 (APOH), and clusterin (CLUS) were found to be up-regulated in the PNR and Rs groups whereas their levels displayed no changes in the Rm group when compared to baseline samples. Additionally, leucine-rich alpha-2-glycoprotein (A2GL), vitamin D-binding protein (VTDB), alpha-1B-glycoprotein (A1BG) and complement C1r subcomponent (C1R) were significantly increased in the serum of the Rm group. Through the incorporation of proteomics technologies, novel serum marker-molecules demonstrating high sensitivity and specificity are introduced, hence offering an innovative approach regarding the evaluation of CD patients' response to IFX therapy.
英夫利昔单抗（IFX）显著改善了克罗恩病（CD）的治疗效果。然而，目前仍需要寻找预测因子，以指示患者对 IFX 的反应。在本研究中，我们采用蛋白质组学技术监测接受 IFX 治疗后的患者的蛋白表达差异，旨在确定一组 CD 候选蛋白生物标志物，以作为治疗反应的标志。我们纳入了 18 名患者，他们要么达到了临床和血清学缓解（Rm，n=6），要么达到了反应（Rs，n=6）和/或无应答（PNRs，n=6）。血清样本进行二维凝胶电泳。对密度计数据进行评估后，对各组间差异表达的蛋白点进行进一步的 MALDI-TOF-MS 分析。鉴定出的蛋白质通过免疫印迹分析进行评估，同时进行功能网络关联分析以评估其意义。发现载脂蛋白 A-I（APOA1）、载脂蛋白 E（APOE）、补体 C4-B（CO4B）、纤溶酶原（PLMN）、转铁蛋白（TRFE）、β-2-糖蛋白 1（APOH）和载脂蛋白（CLUS）在 PNR 和 Rs 组中上调，而与基线样本相比，其在 Rm 组中的水平没有变化。此外，富含亮氨酸的α-2-糖蛋白（A2GL）、维生素 D 结合蛋白（VTDB）、α-1B-糖蛋白（A1BG）和补体 C1r 亚基（C1R）在 Rm 组中的血清中显著增加。通过整合蛋白质组学技术，引入了具有高灵敏度和特异性的新型血清标志物分子，为评估 CD 患者对 IFX 治疗的反应提供了一种创新方法。
