Whole Transcription Profile of Responders to Anti-TNF Drugs in Pediatric Inflammatory Bowel Disease
| Autor: | Sara Salvador-Martín, Bartosz Kaczmarczyk, Rebeca Álvarez, Víctor Manuel Navas-López, Carmen Gallego-Fernández, Ana Moreno-Álvarez, Alfonso Solar-Boga, Cesar Sánchez, Mar Tolin, Marta Velasco, Rosana Muñoz-Codoceo, Alejandro Rodriguez-Martinez, Concepción A. Vayo, Ferrán Bossacoma, Gemma Pujol-Muncunill, María J. Fobelo, Antonio Millán-Jiménez, Lorena Magallares, Eva Martínez-Ojinaga, Inés Loverdos, Francisco J. Eizaguirre, José A. Blanca-García, Susana Clemente, Ruth García-Romero, Vicente Merino-Bohórquez, Rafael González de Caldas, Enrique Vázquez, Ana Dopazo, María Sanjurjo-Sáez, Luis A. López-Fernández |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Pharmaceutics, Vol 13, Iss 1, p 77 (2021) |
| Druh dokumentu: | article |
| ISSN: | 13010077 1999-4923 |
| DOI: | 10.3390/pharmaceutics13010077 |
| Popis: | 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 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. |
| Databáze: | Directory of Open Access Journals |
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