Background: Up to 30% of patients with pediatric inflammatory bowel disease (IBD) do not respond to anti-Tumor Necrosis Factor (anti-TNF) therapy. The aim of this study was to identify pharmacogenomic markers that predict early response to anti-TNF drugs in pediatric patients with IBD. Methods: An observational, longitudinal, prospective cohort study was conducted. The study population comprised 38 patients with IBD aged < 18 years who started treatment with infliximab or adalimumab (29 responders and nine non-responders). Whole gene expression profiles from total RNA isolated from whole blood samples of six responders and six non-responders taken before administration of the biologic and after two weeks of therapy were analyzed using next-generation RNA sequencing. The expression of six selected genes was measured for purposes of validation in all of the 38 patients recruited using qPCR. Results: Genes were differentially expressed in non-responders and responders (32 before initiation of treatment and 44 after two weeks, Log2FC (Fold change) >0.6 or <−0.6 and p value < 0.05). After validation, FCGR1A, FCGR1B, and GBP1 were overexpressed in non-responders two weeks after initiation 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.

中文翻译：

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小儿炎症性肠病中抗TNF药物应答者的完整转录谱

背景：多达30％的小儿炎症性肠病（IBD）患者对抗肿瘤坏死因子（anti-TNF）治疗无效。这项研究的目的是确定可预测IBD患儿抗TNF药物早期反应的药物基因组学标记。方法：进行了一项观察性，纵向，前瞻性队列研究。研究人群包括38位年龄小于18岁的IBD患者，他们开始用英夫利昔单抗或阿达木单抗治疗（29位缓解者和9位非缓解者）。使用下一代RNA测序技术分析了在施用生物制剂之前和治疗两周后从六种反应者和六种非反应者的全血样本中分离出的总RNA中的全基因表达谱。为了验证目的，在使用qPCR招募的所有38位患者中测量了6个选定基因的表达。结果：基因在无反应者和无反应者中差异表达（开始治疗前32位，两周后44位，Log2FC（倍数变化）> 0.6或<-0.6和p值<0.05）。验证后，在开始抗TNF治疗后两周，FCGR1A，FCGR1B和GBP1在无反应者中过表达（Log2FC分别为1.05、1.21和1.08，p值<0.05）。结论：FCGR1A，FCGR1B和GBP1基因的表达是儿童IBD中对抗TNF药物早期反应的药物基因组学生物标记。