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肿瘤坏死因子-α基因在结直肠黏膜中的表达作为溃疡性结肠炎患者英夫利昔单抗诱导治疗后缓解的预测指标

TNF-alpha gene expression in colorectal mucosa as a predictor of remission after induction therapy with infliximab in ulcerative colitis.

作者信息

Olsen Trine, Goll Rasmus, Cui Guanglin, Christiansen Ingrid, Florholmen Jon

机构信息

Laboratory of Gastroenterology, Institute of Clinical Medicine, University of Tromsø, Breivika, N-9037 Tromsø, Norway.

出版信息

Cytokine. 2009 May;46(2):222-7. doi: 10.1016/j.cyto.2009.02.001. Epub 2009 Mar 14.

Abstract

BACKGROUND

It has been documented that treatment with infliximab (IFX) induces remission in 1/3 of patients with moderate to severe ulcerative colitis (UC). Predictors of response could improve selection of patients with a higher probability of favorable outcome.

AIM

To determine predictor factors for the clinical outcome of IFX induction therapy in UC.

METHODS

UC patients with moderate to severe disease who received 5mg/kg IFX at weeks 0, 2 and 6weeks were included. Ulcerative colitis disease activity index (UCDAI) score including endoscopic sub-scores were assessed before and after treatment. Several predictors, including TNF-alpha mRNA expression, were tested in a regression model.

RESULTS

Fifty-nine patients completed the study. Age, gender, steroid therapy, immunosuppressive, pancolitis, endoscopic sub-score, disease duration, C-reactive protein, interleukin-(IL)-4, IL-10 or interferon-gamma (IFN-gamma) did not predict mucosal or clinical remission. There was an inverse and independent association between pre-treatment TNF-alpha expression levels and clinical and endoscopic remission of IFX treatment (logistic regression, p=0.01 and p=0.003, odds ratio 2.5 and 4.8, respectively).

CONCLUSION

The clinical outcome of an induction therapy with IFX in UC is inversely associated with the pre-treatment gene expression levels of TNF-alpha in colorectal mucosa.

摘要

背景

已有文献记载,英夫利昔单抗(IFX)治疗可使三分之一的中度至重度溃疡性结肠炎(UC)患者获得缓解。反应预测指标有助于更好地选择可能获得良好预后的患者。

目的

确定UC患者IFX诱导治疗临床结局的预测因素。

方法

纳入中度至重度UC患者,于第0、2和6周接受5mg/kg IFX治疗。治疗前后评估溃疡性结肠炎疾病活动指数(UCDAI)评分,包括内镜亚评分。在回归模型中对包括肿瘤坏死因子-α(TNF-α)mRNA表达在内的多个预测指标进行检测。

结果

59例患者完成研究。年龄、性别、类固醇治疗、免疫抑制、全结肠炎、内镜亚评分、病程、C反应蛋白、白细胞介素-(IL)-4、IL-10或干扰素-γ(IFN-γ)均不能预测黏膜或临床缓解。治疗前TNF-α表达水平与IFX治疗的临床及内镜缓解呈负相关且独立相关(逻辑回归,p=0.01和p=0.003,比值比分别为2.5和4.8)。

结论

UC患者IFX诱导治疗的临床结局与结直肠黏膜TNF-α的治疗前基因表达水平呈负相关。

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