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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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 recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Institut d'Investigació i Innovació Parc Taulí (I3PT)
Repositorio:r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí
OAI Identifier:oai:i3pt.fundanetsuite.com:p2140
Acceso en línea:https://i3pt.portalinvestigacion.com/publicaciones/2140
Access Level:acceso abierto
Palabra clave:biomarker
gene expression
infliximab
adalimumab
ulcerative colitis
Crohn disease
inflammatory bowel disease
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spelling Whole Transcription Profile of Responders to Anti-TNF Drugs in Pediatric Inflammatory Bowel DiseaseSalvador-Martin, SKaczmarczyk, BAlvarez, RNavas-Lopez, VMGallego-Fernandez, CMoreno-Alvarez, ASolar-Boga, ASanchez, CTolin, MVelasco, MMunoz-Codoceo, RRodriguez-Martinez, AVayo, CABossacoma, FPujol-Muncunill, GFobelo, MJMillan-Jimenez, AMagallares, LEva, OLoverdos, IEizaguirre, FJBlanca-Garcia, JAClemente, SGarcia-Romero, RMerino-Bohorquez, Vde Caldas, RGVazquez, EDopazo, ASanjurjo-Saez, MLopez-Fernandez, LAbiomarkergene expressioninfliximabadalimumabulcerative colitisCrohn diseaseinflammatory bowel diseaseBackground: 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.MDPI2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://i3pt.portalinvestigacion.com/publicaciones/2140PharmaceuticsISSN: 19994923reponame:r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulíinstname:Institut d'Investigació i Innovació Parc Taulí (I3PT)Inglésinfo:eu-repo/semantics/openAccessoai:i3pt.fundanetsuite.com:p21402026-06-21T15:30:37Z
dc.title.none.fl_str_mv Whole Transcription Profile of Responders to Anti-TNF Drugs in Pediatric Inflammatory Bowel Disease
title Whole Transcription Profile of Responders to Anti-TNF Drugs in Pediatric Inflammatory Bowel Disease
spellingShingle Whole Transcription Profile of Responders to Anti-TNF Drugs in Pediatric Inflammatory Bowel Disease
Salvador-Martin, S
biomarker
gene expression
infliximab
adalimumab
ulcerative colitis
Crohn disease
inflammatory bowel disease
title_short Whole Transcription Profile of Responders to Anti-TNF Drugs in Pediatric Inflammatory Bowel Disease
title_full Whole Transcription Profile of Responders to Anti-TNF Drugs in Pediatric Inflammatory Bowel Disease
title_fullStr Whole Transcription Profile of Responders to Anti-TNF Drugs in Pediatric Inflammatory Bowel Disease
title_full_unstemmed Whole Transcription Profile of Responders to Anti-TNF Drugs in Pediatric Inflammatory Bowel Disease
title_sort Whole Transcription Profile of Responders to Anti-TNF Drugs in Pediatric Inflammatory Bowel Disease
dc.creator.none.fl_str_mv 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
author Salvador-Martin, S
author_facet 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
author_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv biomarker
gene expression
infliximab
adalimumab
ulcerative colitis
Crohn disease
inflammatory bowel disease
topic biomarker
gene expression
infliximab
adalimumab
ulcerative colitis
Crohn disease
inflammatory bowel disease
description 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.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://i3pt.portalinvestigacion.com/publicaciones/2140
url https://i3pt.portalinvestigacion.com/publicaciones/2140
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Pharmaceutics
ISSN: 19994923
reponame:r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí
instname:Institut d'Investigació i Innovació Parc Taulí (I3PT)
instname_str Institut d'Investigació i Innovació Parc Taulí (I3PT)
reponame_str r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí
collection r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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