Artículo
Gene signatures of early response to anti-TNF drugs in pediatric inflammatory bowel disease
Autor/es | Salvador-Martín, Sara
Raposo-Gutiérrez, Irene Navas-López, Víctor Manuel Gallego-Fernández, Carmen Moreno-álvarez, Ana Solar-Boga, Alfonso Millán Jiménez, Antonio Merino Bohórquez, Vicente López-Fernández, Luis A. |
Departamento | Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología Universidad de Sevilla. Departamento de Farmacología |
Fecha de publicación | 2020 |
Fecha de depósito | 2023-05-18 |
Publicado en |
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Resumen | 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 ... 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. |
Agencias financiadoras | Consejeria de Educacion y Deporte de la Comunidad de Madrid ERDF Funds (FEDER) from the European Commission, "A way of making Europe" Gregorio Maranon Health Research Institute Instituto de Salud Carlos III |
Identificador del proyecto | PEJ16/MED/AI-1260
PRE-2018-2 PI16/00559; PI19/00792 |
Cita | Salvador-Martín, S., Raposo-Gutiérrez, I., Navas-López, V.M., Gallego-Fernández, C., Moreno-álvarez, A., Solar-Boga, A.,...,López-Fernández, L.A. (2020). Gene signatures of early response to anti-TNF drugs in pediatric inflammatory bowel disease. International Journal of Molecular Sciences, 21 (9), 3364. https://doi.org/10.3390/ijms21093364. |
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