Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium.
Inflamm Bowel Dis. 2010 Dec;16(12):2090-8. doi: 10.1002/ibd.21301.
Infliximab (IFX) has become the mainstay of therapy of refractory Crohn's disease (CD). However, a subset of patients shows incomplete or no response to this agent. In this study we investigated whether we could identify a mucosal gene panel to predict (non)response to IFX in CD.
Mucosal biopsies were obtained during endoscopy from 37 patients with active CD (19 Crohn's colitis [CDc] and 18 Crohn's ileitis [CDi]) before and after first IFX treatment. Response was defined based on endoscopic and histologic findings. Total RNA was analyzed with Affymetrix Human Genome U133 Plus 2.0 Arrays. Quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR) was used to confirm microarray data.
At baseline, significant gene expression differences were found between CDc and CDi. For predicting response in CDc, comparative analysis of CDc pretreatment expression profiles identified 697 significant probe sets between CDc responders (n = 12) and CDc nonresponders (n = 7). Class prediction analysis of CDc top 20 and top 5 significant genes allowed complete separation between CDc responders and CDc nonresponders. The CDc top 5 genes were TNFAIP6, S100A8, IL11, G0S2, and S100A9. Only one patient with CDi completely healed the ileal mucosa. Even using less stringent response criteria, we could not identify a predictive gene panel for IFX responsiveness in CDi.
This study identified a 100% accurate predictive gene signature for (non)response to IFX in CDc, whereas no such a predictive gene set could be identified for CDi.
英夫利昔单抗（IFX）已成为治疗难治性克罗恩病（CD）的主要方法。然而，有一部分患者对此药物反应不完全或无反应。在这项研究中，我们研究了是否可以确定一个黏膜基因谱来预测 CD 患者对 IFX 的（无）反应。
在 IFX 首次治疗前和治疗后，通过内镜从 37 例活动期 CD 患者（19 例克罗恩结肠炎[CDc]和 18 例克罗恩回肠炎[CDi]）中获取黏膜活检组织。根据内镜和组织学检查结果来定义反应。使用 Affymetrix Human Genome U133 Plus 2.0 Arrays 分析总 RNA。使用定量实时逆转录聚合酶链反应（RT-PCR）来验证微阵列数据。
在基线时，CDc 和 CDi 之间存在明显的基因表达差异。为了预测 CDc 的反应，对 CDc 治疗前的表达谱进行比较分析，在 CDc 应答者（n=12）和 CDc 无应答者（n=7）之间发现了 697 个显著的探针集。对 CDc 前 20 和前 5 个显著基因的分类预测分析，可完全区分 CDc 应答者和 CDc 无应答者。CDc 的前 5 个基因是 TNFAIP6、S100A8、IL11、G0S2 和 S100A9。仅有 1 例 CDi 患者的回肠黏膜完全愈合。即使使用不那么严格的反应标准，我们也无法确定 CDi 对 IFX 反应的预测基因谱。
本研究确定了一个 100%准确的预测 CDc 对 IFX 的（无）反应的基因特征，但对于 CDi，尚未确定这样的预测基因集。
