Crohn's disease (CD) is a chronic immune-mediated disorder for which there is not a fully effective treatment. Moreover, biological therapy with anti-tumor necrosis factor-α (anti-TNF-α) monoclonal antibodies leads to an effective response in only 60–70% of patients. Our previous data suggested that specific loci polymorphism of the TNFRSF1B, FCGR3A, IL1R, IL1B, and FAS genes could be a predictor of the primary non-response to anti-TNF therapy in CD patients. In this work, we propose to explain this hypothesis by functional analysis in colon biopsies and in a cell culture model. Using the RT-qPCR analysis, we estimated the FCGR3A, IL1R, TNFRSF1B, IL1B, FAS, and ADAM17 genes mRNA level in colon biopsies material from inflamed and non-inflamed tissue from 21 CD patients (14 responders and 7 non-responders to anti-TNF therapy) and 6 controls, as well as in vitro in a peripheral blood mononuclear cells (PBMCs) from 14 CD patients (seven responders and seven non-responders to anti-TNF therapy) and eight controls cultured for 72 h with 10 μg/ml of anti-TNF antibody. Our findings demonstrated a significant down-regulation of TNFRSF1B gene expression in non-responders both in inflamed and in non-inflamed colon tissue, while the expression of the FCGR3A and IL1B genes was significantly up-regulated in non-responders in the inflamed colon region. In vitro research results indicate that the anti-TNF drug induced a significant decrease in TNFRSF1B, FCGR3A, and FAS gene expression in non-responders. These results show that altered TNFRSF1B, FCGR3A, and IL1B genes expression can be a predictor of the primary non-response to anti-TNF therapy in CD patients.

克罗恩病（CD）是一种慢性免疫介导的疾病，目前尚无完全有效的治疗方法。此外，抗肿瘤坏死因子-α（anti-TNF-α）单克隆抗体的生物疗法仅在60-70％的患者中产生有效的反应。我们之前的数据表明，具体位点 的多态性 TNFRSF1B，FCGR3A，IL1R，IL1B， 和 财务会计这些基因可能是CD患者抗TNF治疗的主要反应。在这项工作中，我们建议通过结肠活检和细胞培养模型中的功能分析来解释这一假设。使用RT-qPCR分析，我们估算了FCGR3A，IL1R，TNFRSF1B，IL1B，FAS， 和 ADAM17 来自21位CD患者的炎症和非炎症组织的结肠活检材料中的基因mRNA水平（14位反应者和7位对TNF治疗无反应的患者）和6位对照，以及 体外分别来自14位CD患者的外周血单核细胞（PBMC）（七名反应者和七名无反应者对抗TNF治疗）和八名对照，分别用10μg/ ml的抗TNF抗体培养72小时。我们的研究结果表明，该蛋白的显着下调TNFRSF1B 基因表达在发炎和未发炎的结肠组织中无反应者中，而 FCGR3A 和 白介素1B 在发炎的结肠区域的无反应者中，这些基因显着上调。 体外 研究结果表明，抗TNF药物可显着降低 TNFRSF1B，FCGR3A， 和 财务会计基因在无反应者中的表达。这些结果表明，TNFRSF1B，FCGR3A， 和 白介素1B 基因表达可以预测CD患者抗TNF治疗的主要反应。