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


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.

SUBMITTER: Salvador-Martin S 

PROVIDER: S-EPMC7247673 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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

Salvador-Martín Sara S   Raposo-Gutiérrez Irene I   Navas-López Víctor Manuel VM   Gallego-Fernández Carmen C   Moreno-Álvarez Ana A   Solar-Boga Alfonso A   Muñoz-Codoceo Rosana R   Magallares Lorena L   Martínez-Ojinaga Eva E   Fobelo María J MJ   Millán-Jiménez Antonio A   Rodriguez-Martinez Alejandro A   Vayo Concepción A CA   Sánchez Cesar C   Tolin Mar M   Bossacoma Ferrán F   Pujol-Muncunill Gemma G   González de Caldas Rafael R   Loverdos Inés I   Blanca-García José A JA   Segarra Oscar O   Eizaguirre Francisco J FJ   García-Romero Ruth R   Merino-Bohórquez Vicente V   Sanjurjo-Sáez María M   López-Fernández Luis A LA  

International journal of molecular sciences 20200509 9


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 res  ...[more]

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