Whole Transcription Profile of Responders to Anti-TNF Drugs in Pediatric Inflammatory Bowel Disease

Pharmaceutics

Gemma Pujol-Muncunill¹  Rosana Muñoz-Codoceo²  Marta Velasco²  Lorena Magallares³  Eva Martínez-Ojinaga³  Ferrán Bossacoma⁴  Mar Tolin⁵  Cesar Sánchez⁵  Rebeca Álvarez⁶  Ana Dopazo⁶  Enrique Vázquez⁶  Ana Moreno-Álvarez⁷  Alfonso Solar-Boga⁷  Ruth García-Romero⁸  JoséA. Blanca-García⁹  Rafael González de Caldas^1,10  FranciscoJ. Eizaguirre^1,11  Antonio Millán-Jiménez^1,12  VíctorManuel Navas-López^1,13  Alejandro Rodriguez-Martinez^1,14  Inés Loverdos^1,15  Carmen Gallego-Fernández^1,16  Sara Salvador-Martín^1,17  Bartosz Kaczmarczyk^1,17  LuisA. López-Fernández^1,17  María Sanjurjo-Sáez^1,17  ConcepciónA. Vayo^1,18  MaríaJ. Fobelo^1,19  Susana Clemente^2,20  Vicente Merino-Bohórquez^2,21 

[1] Department of Pediatric Gastroenterology, Hepatology and Nutrition, Hospital Sant Joan de Déu, 08950 Barcelona, Spain;Department of Pediatric Gastroenterology, Hospital Infantil Universitario Niño Jesús, 28009 Madrid, Spain;Department of Pediatric Gastroenterology, University Hospital La Paz, 28046 Madrid, Spain;Fundació Sant Joan de Déu, Fundació Salut Emporda, 08950 Barcelona, Spain;Gastroenterology Unit, Instituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, 28007 Madrid, Spain;Genomics Unit, Spanish Nacional Center for Cardiovascular Diseases (CNIC), 28029 Madrid, Spain;Pediatric Gastroenterology Unit, Department of Pediatrics, A Coruña University Hospital, 15006 A Coruña, Spain;Pediatric Gastroenterology Unit, Hospital Infantil Miguel Servet, 50009 Zaragoza, Spain;Pediatric Gastroenterology Unit, Hospital Puerta del Mar, 11009 Cadiz, Spain;Pediatric Gastroenterology Unit, Hospital Reina Sofía, 14004 Córdoba, Spain;Pediatric Gastroenterology Unit, Hospital Universitario Donostia, 20014 San Sebastián, Spain;Pediatric Gastroenterology Unit, Hospital Virgen de Valme, 41014 Sevilla, Spain;Pediatric Gastroenterology and Nutrition Unit, Hospital Regional Universitario de Málaga, IBIMA Multidisciplinary Group for Pediatric Research, 29010 Málaga, Spain;Pediatric Gastroenterology, Hepatology and Nutrition Unit, Hospital Universitario Virgen del Rocio, 41013 Seville, Spain;Pediatric Gastroenterology, Hepatology and Nutrition Unit, Hospital de Sabadell, Corporació Sanitària Universitària Parc Taulí, 08208 Barcelona, Spain;Pharmacy Department, Hospital Regional Universitario de Málaga, 29010 Málaga, Spain;Pharmacy Department, Instituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, 28007 Madrid, Spain;Pharmacy Service, Hospital Universitario Virgen del Rocio, 41013 Seville, Spain;Pharmacy Service, Hospital Virgen de Valme, 41014 Sevilla, Spain;Pharmacy Unit, Hospital Universitario Vall d’Hebrón, 08035 Barcelona, Spain;UGC Pharmacy Department, Hospital Virgen de la Macarena, 41009 Sevilla, Spain;

关键词: biomarker;    gene expression;    infliximab;    adalimumab;    ulcerative colitis;    Crohn disease;   

DOI  :  10.3390/pharmaceutics13010077

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown