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Whole Transcription Profile of Responders to Anti-TNF Drugs in Pediatric Inflammatory Bowel Disease Kaczmarczyk, Bartosz Álvarez, Rebeca Navas-López, Víctor Manuel Gallego-Fernández, Carmen Moreno-Álvarez, Ana Clemente Bautista, Susana Salvador-Martín, Sara Institut Català de la Salut [Salvador-Martín S, Kaczmarczyk B] Pharmacy Department, Instituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, 28007 Madrid, Spain. [Álvarez R] Genomics Unit, Spanish Nacional Center for Cardiovascular Diseases (CNIC), 28029 Madrid, Spain. [Navas-López VM] Pediatric Gastroenterology and Nutrition Unit, Hospital Regional Universitario de Málaga, IBIMA Multidisciplinary Group for Pediatric Research, 29010 Málaga, Spain. [Gallego-Fernández C] Pharmacy Department, Hospital Regional Universitario de Málaga, 29010 Málaga, Spain. [Moreno-Álvarez A] Pediatric Gastroenterology Unit, Department of Pediatrics, A Coruña University Hospital, 15006 A Coruña, Spain. [Clemente S] Servei de Farmàcia, Vall d’Hebron Hospital Universitari, Barcelona, Spain Vall d'Hebron Barcelona Hospital Campus Intestins - Inflamació Medicaments - Administració Adolescents DISEASES::Digestive System Diseases::Gastrointestinal Diseases::Gastroenteritis::Inflammatory Bowel Diseases Other subheadings::Other subheadings::Other subheadings::/drug therapy NAMED GROUPS::Persons::Age Groups::Adolescent ENFERMEDADES::enfermedades del sistema digestivo::enfermedades gastrointestinales::gastroenteritis::enfermedad inflamatoria intestinal Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia DENOMINACIONES DE GRUPOS::personas::Grupos de Edad::adolescente Biomarcador; Expressió gènica; Malaltia inflamatòria intestinal Biomarcador; Expresión génica; Enfermedad inflamatoria intestinal Biomarker; Gene expression; 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 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 <−0.6 and 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. This research was funded by Instituto de Salud Carlos III (grants numbers PI16/00559 and PI19/00792), Consejería de Educación y Deporte de la Comunidad de Madrid (grant number PEJ16/MED/AI-1260), and by the Gregorio Marañón Health Research Institute (grant number PRE-2018-2). The study was cofunded by European Regional Develompment Funds (FEDER) from the European Commission, “A way of making Europe”. 2021-05-17T12:17:43Z 2021-05-17T12:17:43Z 2021-01-08 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Salvador-Martín S, Kaczmarczyk B, Álvarez R, Navas-López VM, Gallego-Fernández C, Moreno-Álvarez A, et al. Whole Transcription Profile of Responders to Anti-TNF Drugs in Pediatric Inflammatory Bowel Disease. Pharmaceutics. 2021 Jan 8;13(1):77. 1999-4923 https://hdl.handle.net/11351/5958 10.3390/pharmaceutics13010077 33429950 000610704100001 http://hdl.handle.net/11351/5958 eng Pharmaceutics;13(1) https://doi.org/10.3390/pharmaceutics13010077 info:eu-repo/grantAgreement/ES/PE2013-2016/PI16%2F00559 info:eu-repo/grantAgreement/ES/PE2017-2020/PI19%2F00792 info:eu-repo/grantAgreement/ES/PE2013-2016/PEJ16%2FMED%2FAI-1260 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess application/pdf MDPI Scientia