Gene Signatures of Early Response to Anti-TNF Drugs in Pediatric Inflammatory Bowel Disease

Around a 20-30% of inflammatory bowel disease (IBD) patients are diagnosed before they are 18 years old. Anti-TNF drugs can induce and maintain remission in IBD, however, up to 30% of patients do not respond. The aim of the work was to identify markers that would predict an early response to anti-TN...

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Detalhes bibliográficos
Autores: Salvador-Martin, S, Raposo-Gutierrez, I, Navas-Lopez, VM, Gallego-Fernandez, C, Moreno-Alvarez, A, Solar-Boga, A, Munoz-Codoceo, R, Magallares, L, Martinez-Ojinaga, E, Fobelo, MJ, Millan-Jimenez, A, Rodriguez-Martinez, A, Vayo, CA, Sanchez, C, Tolin, M, Bossacoma, F, Pujol-Muncunill, G, de Caldas, RG, Loverdos, I, Blanca-Garcia, JA, Segarra, O, Eizaguirre, FJ, Garcia-Romero, R, Merino-Bohorquez, V, Sanjurjo-Saez, M, Lopez-Fernandez, LA
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Recursos: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:p2650
Acesso em linha:https://i3pt.portalinvestigacion.com/publicaciones/2650
Access Level:acceso abierto
Palavra-chave:biomarker
gene expression
infliximab
adalimumab
ulcerative colitis
Crohn's disease
Descrição
Resumo:Around a 20-30% of inflammatory bowel disease (IBD) patients are diagnosed before they are 18 years old. Anti-TNF drugs can induce and maintain remission in IBD, however, up to 30% of patients do not respond. The aim of the work was to identify markers that would predict an early response to anti-TNF drugs in pediatric patients with IBD. The study population included 43 patients aged <18 years with IBD who started treatment with infliximab or adalimumab. Patients were classified into primary responders (n = 27) and non-responders to anti-TNF therapy (n = 6). Response to treatment could not be analyzed in 10 patients. Response was defined as a decrease in over 15 points in the disease activity indexes from week 0 to week 10 of infliximab treatment or from week 0 to week 26 of adalimumab treatment. The expression profiles of nine genes in total RNA isolated from the whole-blood of pediatric IBD patients taken before biologic administration and after 2 weeks were analyzed using qPCR and the 2(-Ct) method. Before initiation and after 2 weeks of treatment the expression of SMAD7 was decreased in patients who were considered as non-responders (p value < 0.05). Changes in expression were also observed for TLR2 at T0 and T2, although that did not reach the level of statistical significance. In addition, the expression of DEFA5 decreased 1.75-fold during the first 2 weeks of anti-TNF treatment in responders, whereas no changes were observed in non-responders. Expression of the SMAD7 gene is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBD. TLR2 and DEFA5 need to be validated in larger studies.

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