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Int J Mol Sci ; 21(9)2020 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-32397546

RESUMO

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.


Assuntos
Adalimumab/farmacologia , Anti-Inflamatórios/farmacologia , Antirreumáticos/farmacologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/farmacologia , Transcriptoma/efeitos dos fármacos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab/uso terapêutico , Adolescente , Anti-Inflamatórios/uso terapêutico , Antirreumáticos/uso terapêutico , Criança , Pré-Escolar , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Lactente , Doenças Inflamatórias Intestinais/sangue , Doenças Inflamatórias Intestinais/genética , Infliximab/uso terapêutico , Masculino , RNA Mensageiro/biossíntese , RNA Mensageiro/sangue , RNA Mensageiro/genética , Receptores Tipo II do Fator de Necrose Tumoral/biossíntese , Receptores Tipo II do Fator de Necrose Tumoral/genética , Proteína Smad7/biossíntese , Proteína Smad7/genética , Receptor 2 Toll-Like/biossíntese , Receptor 2 Toll-Like/genética , Resultado do Tratamento , Receptor Gatilho 1 Expresso em Células Mieloides/biossíntese , Receptor Gatilho 1 Expresso em Células Mieloides/genética , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/genética , alfa-Defensinas/biossíntese , alfa-Defensinas/genética
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