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

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 o...

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Detalhes bibliográficos
Autores: Salvador-Martin, S, Kaczmarczyk, B, Alvarez, R, Navas-Lopez, VM, Gallego-Fernandez, C, Moreno-Alvarez, A, Solar-Boga, A, Sanchez, C, Tolin, M, Velasco, M, Munoz-Codoceo, R, Rodriguez-Martinez, A, Vayo, CA, Bossacoma, F, Pujol-Muncunill, G, Fobelo, MJ, Millan-Jimenez, A, Magallares, L, Eva, O, Loverdos, I, Eizaguirre, FJ, Blanca-Garcia, JA, Clemente, S, Garcia-Romero, R, Merino-Bohorquez, V, de Caldas, RG, Vazquez, E, Dopazo, A, Sanjurjo-Saez, M, Lopez-Fernandez, LA
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2021
País:España
Recursos:Institut d'Investigació i Innovació Parc Taulí (I3PT)
Repositório:r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí
OAI Identifier:oai:i3pt.fundanetsuite.com:p2140
Acesso em linha:https://i3pt.portalinvestigacion.com/publicaciones/2140
Access Level:Acceso aberto
Palavra-chave:biomarker
gene expression
infliximab
adalimumab
ulcerative colitis
Crohn disease
inflammatory bowel disease
Descrição
Resumo: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.

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