Gene Signatures of Early Response to Anti-TNF Drugs in Pediatric Inflammatory Bowel Disease

International Journal of Molecular Sciences

Gemma Pujol-Muncunill¹  Rosana Muñoz-Codoceo²  Lorena Magallares³  Eva Martínez-Ojinaga³  Ferrán Bossacoma⁴  Mar Tolin⁵  Cesar Sánchez⁵  Ana Moreno-Álvarez⁶  Alfonso Solar-Boga⁶  Ruth García-Romero⁷  José A. Blanca-García⁸  Rafael González de Caldas⁹  Francisco J. Eizaguirre^1,10  Oscar Segarra^1,11  Antonio Millán-Jiménez^1,12  Víctor Manuel Navas-López^1,13  Alejandro Rodriguez-Martinez^1,14  Inés Loverdos^1,15  Sara Salvador-Martín^1,16  Irene Raposo-Gutiérrez^1,16  Luis A. López-Fernández^1,16  María Sanjurjo-Sáez^1,16  Carmen Gallego-Fernández^1,17  Concepción A. Vayo^1,18  María J. Fobelo^1,19  Vicente Merino-Bohórquez^2,20 

[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, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, 28007 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 Universitario Vall d’Hebrón, 08035 Barcelona, 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 General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, 28007 Madrid, Spain;Pharmacy Department, Hospital Regional Universitario de Málaga, 29010 Málaga, Spain;Pharmacy Service, Hospital Universitario Virgen del Rocio, 41013 Seville, Spain;Pharmacy Service, Hospital Virgen de Valme, 41014 Sevilla, Spain;UGC Pharmacy Department, Hospital Virgen de la Macarena, 41009 Sevilla, Spain;

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

DOI  :  10.3390/ijms21093364

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown