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抗 TNF 药物治疗小儿炎症性肠病早期反应的基因特征。

Gene Signatures of Early Response to Anti-TNF Drugs in Pediatric Inflammatory Bowel Disease.

机构信息

Pharmacy Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, 28007 Madrid, Spain.

Pediatric Gastroenterology and Nutrition Unit, Hospital Regional Universitario de Málaga, IBIMA Multidisciplinary Group for Pediatric Research, 29010 Málaga, Spain.

出版信息

Int J Mol Sci. 2020 May 9;21(9):3364. doi: 10.3390/ijms21093364.

Abstract

Around a 20-30% of inflammatory bowel disease (IBD) patients are diagnosed before they are 18 years old. Anti-TNF drugs can induce and maintain remission in IBD, however, up to 30% of patients do not respond. The aim of the work was to identify markers that would predict an early response to anti-TNF drugs in pediatric patients with IBD. The study population included 43 patients aged <18 years with IBD who started treatment with infliximab or adalimumab. Patients were classified into primary responders ( = 27) and non-responders to anti-TNF therapy ( = 6). Response to treatment could not be analyzed in 10 patients. Response was defined as a decrease in over 15 points in the disease activity indexes from week 0 to week 10 of infliximab treatment or from week 0 to week 26 of adalimumab treatment. The expression profiles of nine genes in total RNA isolated from the whole-blood of pediatric IBD patients taken before biologic administration and after 2 weeks were analyzed using qPCR and the 2 method. Before initiation and after 2 weeks of treatment the expression of was decreased in patients who were considered as non-responders ( value < 0.05). Changes in expression were also observed for at T0 and T2, although that did not reach the level of statistical significance. In addition, the expression of decreased 1.75-fold during the first 2 weeks of anti-TNF treatment in responders, whereas no changes were observed in non-responders. Expression of the gene is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBD. and need to be validated in larger studies.

摘要

大约有 20-30%的炎症性肠病 (IBD) 患者在 18 岁之前被诊断出来。抗 TNF 药物可以诱导和维持 IBD 的缓解,但多达 30%的患者没有反应。本研究旨在确定标记物,以预测儿科 IBD 患者对抗 TNF 药物的早期反应。研究人群包括 43 名年龄<18 岁的 IBD 患者,他们开始接受英夫利昔单抗或阿达木单抗治疗。患者分为抗 TNF 治疗的原发性应答者(=27)和无应答者(=6)。有 10 名患者无法分析治疗反应。反应定义为英夫利昔单抗治疗第 0 周至第 10 周或阿达木单抗治疗第 0 周至第 26 周时疾病活动指数下降超过 15 分。使用 qPCR 和 2 法分析了生物制剂治疗前和治疗后 2 周采集的儿科 IBD 患者全血总 RNA 中 9 个基因的表达谱。在开始治疗前和治疗后 2 周,被认为无应答者的患者的 表达下降( 值<0.05)。在 T0 和 T2 时也观察到 的表达变化,尽管未达到统计学意义。此外,在应答者中,在抗 TNF 治疗的前 2 周内, 的表达下降了 1.75 倍,而无应答者没有变化。 的表达是儿科 IBD 对抗 TNF 药物早期反应的药物基因组生物标志物。 和 需要在更大的研究中验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9014/7247673/225da1484144/ijms-21-03364-g001.jpg

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