Salvador-Martín, SaraRaposo-Gutiérrez, IreneNavas-López, Víctor ManuelGallego-Fernández, CarmenMoreno-Álvarez, AnaSolar-Boga, AlfonsoMuñoz-Codoceo, RosanaMagallares, LorenaMartínez-Ojinaga, EvaFobelo, María J.Millán-Jiménez, AntonioRodriguez-Martinez, AlejandroVayo, Concepción A.Sánchez, CesarTolin, MarBossacoma, FerránPujol-Muncunill, GemmaGonzález de Caldas, RafaelLoverdos, InésBlanca-García, José A.Segarra, OscarEizaguirre, Francisco J.García-Romero, RuthMerino-Bohórquez, VicenteSanjurjo-Sáez, MaríaLópez-Fernández, Luis A.2022-06-222022-06-222020-05-09Salvador-Martín S, Raposo-Gutiérrez I, Navas-López VM, Gallego-Fernández C, Moreno-Álvarez A, Solar-Boga A, et al. Gene Signatures of Early Response to Anti-TNF Drugs in Pediatric Inflammatory Bowel Disease. Int J Mol Sci. 2020 May 9;21(9):3364http://hdl.handle.net/10668/3700Around 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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/BiomarkerGene expressionInfliximabAdalimumabUlcerative colitisCrohn’s diseaseBiomarcadoresExpresión génicaColitis ulcerosaEnfermedad de CrohnMedical Subject Headings::Persons::Persons::Age Groups::AdolescentMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Inflammatory AgentsMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antirheumatic AgentsMedical Subject Headings::Persons::Persons::Age Groups::ChildMedical Subject Headings::Persons::Persons::Age Groups::Child::Child, PreschoolMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression RegulationMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Persons::Persons::Age Groups::InfantMedical Subject Headings::Diseases::Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Inflammatory Bowel DiseasesMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, MessengerMedical Subject Headings::Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Antigens, Differentiation::Antigens, CD::Receptors, Tumor Necrosis Factor, Type IIMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Carrier Proteins::Adaptor Proteins, Signal Transducing::Smad Proteins::Smad Proteins, Inhibitory::Smad7 ProteinMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Receptors, Pattern Recognition::Toll-Like ReceptorsMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression::Transcription, Genetic::TranscriptomeMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment OutcomeMedical Subject Headings::Chemicals and Drugs::Biological Factors::Intercellular Signaling Peptides and Proteins::Tumor Necrosis Factors::Tumor Necrosis Factor-alphaMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Antimicrobial Cationic Peptides::Defensins::alpha-Defensinsresearch article32397546open access10.3390/ijms210933641422-0067PMC7247673