Serum miRNAs Are Pharmacodynamic Biomarkers Associated With Therapeutic Response in Pediatric Inflammatory Bowel Disease.
Inflamm Bowel Dis
; 26(10): 1597-1606, 2020 09 18.
Article
em En
| MEDLINE
| ID: mdl-32793975
ABSTRACT
BACKGROUND:
We sought to identify microRNAs (miRNAs) associated with response to anti-TNF-α or glucocorticoids in children with inflammatory bowel disease (IBD) to generate candidate pharmacodynamic and monitoring biomarkers.METHODS:
Clinical response was assessed by Pediatric Crohn's Disease Activity Index and Pediatric Ulcerative Colitis Activity Index. Quantitative real-time polymerase chain reaction via Taqman Low-Density Array cards were used to identify miRNAs in a discovery cohort of responders (nâ =â 11) and nonresponders (nâ =â 8). Seven serum miRNAs associated with clinical response to treatment, along with 4 previously identified (miR-146a, miR-146b, miR-320a, miR-486), were selected for further study. Candidates were assessed in a validation cohort of serum samples from IBD patients pre- and post-treatment and from healthy controls. Expression of miRNA was also analyzed in inflamed mucosal biopsies from IBD patients and non-IBD controls.RESULTS:
Discovery cohort analysis identified 7 miRNAs associated with therapeutic response 5 that decreased (miR-126, miR-454, miR-26b, miR-26a, let-7c) and 2 that increased (miR-636, miR-193b). In the validation cohort, 7 of 11 candidate miRNAs changed in the same direction with response to anti-TNF-α therapies, glucocorticoids, or both. In mucosal biopsies, 7 out of 11 miRNAs were significantly increased in IBD vs healthy controls.CONCLUSIONS:
Five candidate miRNAs associated with clinical response and mucosal inflammation in pediatric IBD patients were identified (miR-126, let-7c, miR-146a, miR-146b, and miR-320a). These miRNAs may be further developed as pharmacodynamic and response monitoring biomarkers for use in clinical care and trials.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Colite Ulcerativa
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Doença de Crohn
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Monitoramento de Medicamentos
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MicroRNAs
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Inibidores do Fator de Necrose Tumoral
Tipo de estudo:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adolescent
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Adult
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Child
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Child, preschool
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article