Gene signatures of early response to anti-TNF drugs in pediatric inflammatory bowel disease

T. 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...

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Detalles Bibliográficos
Autores: Salvador-Martín, Sara, Raposo-Gutiérrez, Irene, Navas-López, Víctor Manuel, Gallego-Fernández, Carmen, Moreno-Álvarez, Ana, Solar-Boga, Alfonso, Muñoz Codoceo, Rosa Ana, Magallares, Lorena, Martínez-Ojinaga, Eva, Fobelo, María J., Millán-Jiménez, Antonio, Rodriguez-Martinez, Alejandro, Vayo, Concepción A., Sánchez, Cesar, Tolin, Mar, Bossacoma, Ferrán, Pujol-Muncunill, Gemma, González de Caldas, Rafael, Loverdos, Inés, Blanca-García, José A., Segarra, Oscar, Eizaguirre, Francisco J., García-Romero, Ruth, Merino-Bohórquez, Vicente, Sanjurjo-Sáez, María, López-Fernández, Luis A.
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/693627
Acceso en línea:http://hdl.handle.net/10486/693627
https://dx.doi.org/10.3390/ijms21093364
Access Level:acceso abierto
Palabra clave:Adalimumab
Biomarker
Crohn’s disease
Gene expression
Infliximab
Ulcerative colitis
Medicina
Descripción
Sumario:T. 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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