Meuwis Marie-Alice, Fillet Marianne, Lutteri Laurence, Marée Raphaël, Geurts Pierre, de Seny Dominique, Malaise Michel, Chapelle Jean-Paul, Wehenkel Louis, Belaiche Jacques, Merville Marie-Paule, Louis Edouard
Laboratory of Clinical Chemistry, GIGA Research, University of Liège, Belgium.
Clin Biochem. 2008 Aug;41(12):960-7. doi: 10.1016/j.clinbiochem.2008.04.021. Epub 2008 May 6.
Infliximab is the first anti-TNFalpha accepted by the Food and Drug Administration for use in inflammatory bowel disease treatment. Few clinical, biological and genetic factors tend to predict response in Crohn's disease (CD) patient subcategories, none widely predicting response to infliximab.
Twenty CD patients showing clinical response or non response to infliximab were used for serum proteomic profiling on Surface Enhanced Lazer Desorption Ionisation-Time of Flight-Mass Spectrometry (SELDI-TOF-MS), each before and after treatment. Univariate and multivariate data analysis were performed for prediction and characterization of response to infliximab.
We obtained a model of classification predicting response to treatment and selected relevant potential biomarkers, among which platelet aggregation factor 4 (PF4). We quantified PF4, sCD40L and IL-6 by ELISA for correlation studies.
This first proteomic pilot study on response to infliximab in CD suggests association between platelet metabolism and response to infliximab and requires validation studies on a larger cohort of patients.
英夫利昔单抗是首个被美国食品药品监督管理局批准用于治疗炎症性肠病的抗肿瘤坏死因子α药物。很少有临床、生物学和基因因素能够预测克罗恩病（CD）患者亚组对英夫利昔单抗的反应，尚无因素能广泛预测对英夫利昔单抗的反应。
选取20例对英夫利昔单抗有临床反应或无反应的CD患者，在治疗前后分别用表面增强激光解吸电离飞行时间质谱（SELDI-TOF-MS）进行血清蛋白质组分析。进行单变量和多变量数据分析，以预测和表征对英夫利昔单抗的反应。
我们获得了一个预测治疗反应的分类模型，并筛选出了相关的潜在生物标志物，其中包括血小板聚集因子4（PF4）。我们通过酶联免疫吸附测定法（ELISA）对PF4、可溶性CD40配体（sCD40L）和白细胞介素-6（IL-6）进行定量，以进行相关性研究。
这项关于CD患者对英夫利昔单抗反应的首次蛋白质组学初步研究表明，血小板代谢与对英夫利昔单抗的反应之间存在关联，需要在更大规模的患者队列中进行验证研究。
