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

Fecha de publicación:

Autores de I3PT

Participantes ajenos a I3PT

  • Salvador-Martin, S
  • Raposo-Gutierrez, I
  • Navas-Lopez, VM
  • Gallego-Fernandez, C
  • Moreno-Alvarez, A
  • Solar-Boga, A
  • Munoz-Codoceo, R
  • Magallares, L
  • Martinez-Ojinaga, E
  • Fobelo, MJ
  • Millan-Jimenez, A
  • Rodriguez-Martinez, A
  • Vayo, CA
  • Sanchez, C
  • Tolin, M
  • Bossacoma, F
  • Pujol-Muncunill, G
  • de Caldas, RG
  • Blanca-Garcia, JA
  • Segarra, O
  • Eizaguirre, FJ
  • Garcia-Romero, R
  • Merino-Bohorquez, V
  • Sanjurjo-Saez, M
  • Lopez-Fernandez, LA

Grupos de Investigación

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.

Datos de la publicación

ISSN/ISSNe:
1661-6596, 1422-0067

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES  MDPI

Tipo:
Article
Páginas:
-
PubMed:
32397546

Citas Recibidas en Web of Science: 19

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Keywords

  • biomarker; gene expression; infliximab; adalimumab; ulcerative colitis; Crohn's disease

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