Whole transcription profile of responders to anti-TNF drugs in pediatric inflammatory bowel disease. Whole transcription profile of responders to anti-TNF drugs in pediatric inflammatory bowel disease

Background: In pediatric inflammatory bowel disease (IBD) up to 30% of patients do not respond to anti-TNF therapy. The aim was to identify pharmacogenomic markers that predict early response to anti-TNF drugs in pediatric patients with IBD. Methods: The study population included 29 responders and 9 non-responders to anti-TNF therapy patients aged 0.6 o <-0.6 and p value < 0.05). After validation, FCGR1A, FCGR1B and GBP1 were overexpressed in non-responders after 2 weeks of anti-TNF treatment (Log2FC 1.05, 1.21 and 1.08, respectively, p value <0.05,); Conclusion: Expression of the FCGR1A, FCGR1B, and GBP1 genes is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBD. Overall design: Whole gene expression profiles from total RNA isolated from whole-blood samples of 6 responders and 6 non-responders taken before biologic administration and after 2 weeks were analyzed by RNA next-generation sequencing.

背景：在儿童炎症性肠病（inflammatory bowel disease, IBD）患者中，高达30%的人群对抗肿瘤坏死因子（anti-TNF）治疗无应答。本研究旨在筛选可预测儿童IBD患者对抗TNF药物早期应答的药物基因组学标志物。
方法：本研究队列纳入29例抗TNF治疗应答者与9例无应答者，受试患者年龄为0.6 o <-0.6（原文存在输入笔误）且p值<0.05。经过验证后，在抗TNF治疗2周后的无应答者体内，FCGR1A、FCGR1B与GBP1基因呈现过表达（Log2倍数变化分别为1.05、1.21与1.08，p值均<0.05）。
结论：FCGR1A、FCGR1B及GBP1基因的表达水平可作为儿童IBD患者对抗TNF制剂早期应答的药物基因组学生物标志物。
整体实验设计：本研究通过RNA下一代测序（RNA next-generation sequencing）技术，对6例抗TNF治疗应答者与6例无应答者在生物制剂给药前及给药2周后采集的全血样本中提取的总RNA进行全基因表达谱分析。