Gene Signatures of Early Response to Anti-TNF Drugs in Pediatric Inflammatory Bowel Disease
Salvador-Martín, Sara; Raposo-Gutiérrez, Irene; Navas-López, Víctor Manuel; Gallego-Fernández, Carmen; Moreno Alvarez, Ana; Solar Boga, Alfonso; Muñoz-Codoceo, Rosana; 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
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Identificadores
URI: http://hdl.handle.net/20.500.11940/16288
PMID: 32397546
DOI: 10.3390/ijms21093364
ISSN: 1661-6596
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Fecha de publicación
2020Título de revista
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Tipo de contenido
Journal Article
DeCS
resultado del tratamiento | enfermedad inflamatoria intestinal | factor de necrosis tumoral alfa | antirreumáticos | regulación de la expresión génica | ARN | transcriptoma | proteína smad7 | humanos | lactante | alfa-defensinas | antiinflamatorios | adolescente | receptor 2 similar a tollMeSH
Inflammatory Bowel Diseases | Toll-Like Receptor 2 | Adolescent | RNA | alpha-Defensins | Anti-Inflammatory Agents | Transcriptome | Tumor Necrosis Factor-alpha | Humans | Antirheumatic Agents | Treatment Outcome | Smad7 Protein | Gene Expression Regulation | InfantResumen
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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