儿童炎症性肠病中抗TNF药物应答者的全转录谱
Whole Transcription Profile of Responders to Anti-TNF Drugs in Pediatric Inflammatory Bowel Disease.
作者信息
Salvador-Martín Sara, Kaczmarczyk Bartosz, Álvarez Rebeca, Navas-López Víctor Manuel, Gallego-Fernández Carmen, Moreno-Álvarez Ana, Solar-Boga Alfonso, Sánchez Cesar, Tolin Mar, Velasco Marta, Muñoz-Codoceo Rosana, Rodriguez-Martinez Alejandro, Vayo Concepción A, Bossacoma Ferrán, Pujol-Muncunill Gemma, Fobelo María J, Millán-Jiménez Antonio, Magallares Lorena, Martínez-Ojinaga Eva, Loverdos Inés, Eizaguirre Francisco J, Blanca-García José A, Clemente Susana, García-Romero Ruth, Merino-Bohórquez Vicente, González de Caldas Rafael, Vázquez Enrique, Dopazo Ana, Sanjurjo-Sáez María, López-Fernández Luis A
机构信息
Pharmacy Department, Instituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, 28007 Madrid, Spain.
Genomics Unit, Spanish Nacional Center for Cardiovascular Diseases (CNIC), 28029 Madrid, Spain.
出版信息
Pharmaceutics. 2021 Jan 8;13(1):77. doi: 10.3390/pharmaceutics13010077.
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 value < 0.05). After validation, , , and were overexpressed in non-responders two weeks after initiation of anti-TNF treatment (Log2FC 1.05, 1.21, and 1.08, respectively, value < 0.05).
CONCLUSION
Expression of the , , and genes is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBD.
背景
高达30%的儿童炎症性肠病（IBD）患者对抗肿瘤坏死因子（anti-TNF）治疗无反应。本研究的目的是确定可预测IBD患儿对anti-TNF药物早期反应的药物基因组学标志物。
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例年龄小于18岁开始使用英夫利昔单抗或阿达木单抗治疗的IBD患者（29例反应者和9例无反应者）。使用下一代RNA测序分析了6例反应者和6例无反应者在生物制剂给药前和治疗两周后从全血样本中分离的总RNA的全基因表达谱。为了验证，使用qPCR测量了所有38例招募患者中6个选定基因的表达。
结果
基因在无反应者和反应者中差异表达（治疗开始前32个，两周后44个，Log2FC（倍数变化）>0.6或<-0.6且P值<0.05）。验证后，anti-TNF治疗开始两周后，无反应者中ANKRD30A、SLC11A1和IFI44L基因过表达（Log2FC分别为1.05、1.21和1.08，P值< 0.05）。
结论
ANKRD30A、SLC11A1和IFI44L基因的表达是儿童IBD中anti-TNF药物早期反应的药物基因组学生物标志物。
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