Whole Transcription Profile of Responders to Anti-TNF Drugs in Pediatric Inflammatory Bowel Disease

• Main Authors: Sara Salvador-Martín (Author), Bartosz Kaczmarczyk (Author), Rebeca Álvarez (Author), Víctor Manuel Navas-López (Author), Carmen Gallego-Fernández (Author), Ana Moreno-Álvarez (Author), Alfonso Solar-Boga (Author), Cesar Sánchez (Author), Mar Tolin (Author), Marta Velasco (Author), Rosana Muñoz-Codoceo (Author), Alejandro Rodriguez-Martinez (Author), Concepción A. Vayo (Author), Ferrán Bossacoma (Author), Gemma Pujol-Muncunill (Author), María J. Fobelo (Author), Antonio Millán-Jiménez (Author), Lorena Magallares (Author), Eva Martínez-Ojinaga (Author), Inés Loverdos (Author), Francisco J. Eizaguirre (Author), José A. Blanca-García (Author), Susana Clemente (Author), Ruth García-Romero (Author), Vicente Merino-Bohórquez (Author), Rafael González de Caldas (Author), Enrique Vázquez (Author), Ana Dopazo (Author), María Sanjurjo-Sáez (Author), Luis A. López-Fernández (Author)
• Format: Book
• Published: MDPI AG, 2021-01-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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 <i>p</i> value < 0.05). After validation, <i>FCGR1A</i>, <i>FCGR1B</i>, and <i>GBP1</i> were overexpressed in non-responders two weeks after initiation of anti-TNF treatment (Log2FC 1.05, 1.21, and 1.08, respectively, <i>p</i> value < 0.05). Conclusion: Expression of the <i>FCGR1A</i>, <i>FCGR1B</i>, and <i>GBP1</i> genes is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBD.

Item Description

10.3390/pharmaceutics13010077
1999-4923