Please use this identifier to cite or link to this item: http://hdl.handle.net/10668/3700
Title: Gene Signatures of Early Response to Anti-TNF Drugs in Pediatric Inflammatory Bowel Disease
Authors: Salvador-Martín, Sara
Raposo-Gutiérrez, Irene
Navas-López, Víctor Manuel
Gallego-Fernández, Carmen
Moreno-Álvarez, 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.
metadata.dc.contributor.authoraffiliation: [Salvador-Martín,S; Raposo-Gutiérrez,I; Sanjurjo-Sáez,M; López-Fernández,LA] Pharmacy Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain. [Navas-López,V] Pediatric Gastroenterology and Nutrition Unit, Hospital Regional Universitario de Málaga, IBIMA Multidisciplinary Group for Pediatric Research, Málaga, Spain. [Gallego-Fernández,C] Pharmacy Department, Hospital Regional Universitario de Málaga, Málaga, Spain. [Moreno-Álvarez,A; Solar-Boga,A] Pediatric Gastroenterology Unit, Department of Pediatrics, A Coruña University Hospital, A Coruña, Spain. [Muñoz-Codoceo,R] Department of Pediatric Gastroenterology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain. [Magallares,L; Martínez-Ojinaga,E] Department of Pediatric Gastroenterology, University Hospital La Paz, Madrid, Spain. [Fobelo,MJ] Pharmacy Service, Hospital Virgen de Valme, Sevilla, Spain. [Millán-Jiménez,A] Pediatric Gastroenterology Unit, Hospital Virgen de Valme, Sevilla, Spain. [Rodriguez-Martinez,A] Pediatric Gastroenterology, Hepatology and Nutrition Unit, Hospital Universitario Virgen del Rocio, Seville, Spain. [Vayo,CA] Pharmacy Service, Hospital Universitario Virgen del Rocio, Seville, Spain. [Sánchez,C; Tolin,M] Gastroenterology Unit, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain. [Bossacoma,F] Fundació Sant Joan de Déu, Fundació Salut Emporda, Barcelona, Spain. [Pujol-Muncunill;G] Department of Pediatric Gastroenterology, Hepatology and Nutrition, Hospital Sant Joan de Déu, Barcelona, Spain. [González de Caldas,R] Pediatric Gastroenterology Unit, Hospital Reina Sofía, Córdoba, Spain. [Loverdos,I] Pediatric Gastroenterology, Hepatology and Nutrition Unit, Hospital de Sabadell, Corporació Sanitària Universitària Parc Taulí, Barcelona, Spain. [Blanca-García,JA] Pediatric Gastroenterology Unit, Hospital Puerta del Mar, Cadiz, Spain. [Segarra,O] Pediatric Gastroenterology Unit, Hospital Universitario Vall d’Hebrón, Barcelona, Spain. [Eizaguirre,FJ] Pediatric Gastroenterology Unit, Hospital Universitario Donostia, San Sebastián, Spain. [García-Romero,R] Pediatric Gastroenterology Unit, Hospital Infantil Miguel Servet, Zaragoza, Spain. [Merino-Bohórquez,V] UGC Pharmacy Department, Hospital Virgen de la Macarena, Sevilla, Spain.
Keywords: Biomarker;Gene expression;Infliximab;Adalimumab;Ulcerative colitis;Crohn’s disease;Biomarcadores;Expresión génica;Colitis ulcerosa;Enfermedad de Crohn
metadata.dc.subject.mesh: Medical Subject Headings::Persons::Persons::Age Groups::Adolescent
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Inflammatory Agents
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antirheumatic Agents
Medical Subject Headings::Persons::Persons::Age Groups::Child
Medical Subject Headings::Persons::Persons::Age Groups::Child::Child, Preschool
Medical Subject Headings::Check Tags::Female
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Persons::Persons::Age Groups::Infant
Medical Subject Headings::Diseases::Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Inflammatory Bowel Diseases
Medical Subject Headings::Check Tags::Male
Medical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Messenger
Medical Subject Headings::Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Antigens, Differentiation::Antigens, CD::Receptors, Tumor Necrosis Factor, Type II
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Carrier Proteins::Adaptor Proteins, Signal Transducing::Smad Proteins::Smad Proteins, Inhibitory::Smad7 Protein
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Receptors, Pattern Recognition::Toll-Like Receptors
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression::Transcription, Genetic::Transcriptome
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment Outcome
Medical Subject Headings::Chemicals and Drugs::Biological Factors::Intercellular Signaling Peptides and Proteins::Tumor Necrosis Factors::Tumor Necrosis Factor-alpha
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Antimicrobial Cationic Peptides::Defensins::alpha-Defensins
Issue Date: 9-May-2020
Publisher: MDPI
Citation: Salvador-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):3364
Abstract: 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.
URI: http://hdl.handle.net/10668/3700
metadata.dc.relation.publisherversion: https://www.mdpi.com/1422-0067/21/9/3364/htm
metadata.dc.identifier.doi: 10.3390/ijms21093364
ISSN: 1422-0067 (Online)
Appears in Collections:01- Artículos - Hospital de Valme
01- Artículos - Hospital Puerta del Mar
01- Artículos - Hospital Regional de Málaga
01- Artículos - Hospital Reina Sofía
01- Artículos - Hospital Virgen del Rocío
01- Artículos - Hospital Virgen Macarena
01- Artículos - IBIMA. Instituto de Investigación Biomédica de Málaga

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