Whole Blood Profiling of T-cell-Derived microRNA Allows the Development of Prognostic models in Inflammatory Bowel Disease.
J Crohns Colitis
; 14(12): 1724-1733, 2020 Dec 02.
Article
em En
| MEDLINE
| ID: mdl-32598439
ABSTRACT
BACKGROUND:
MicroRNAs [miRNAs] are cell-specific small non-coding RNAs that can regulate gene expression and have been implicated in inflammatory bowel disease [IBD] pathogenesis. Here we define the cell-specific miRNA profiles and investigate its biomarker potential in IBD.METHODS:
In a two-stage prospective multi-centre case control study, next generation sequencing was performed on a discovery cohort of immunomagnetically separated leukocytes from 32 patients (nine Crohn's disease [CD], 14 ulcerative colitis [UC], eight healthy controls) and differentially expressed signals were validated in whole blood in 294 patients [97 UC, 98 CD, 98 non-IBD, 1 IBDU] using quantitative PCR. Correlations were analysed with phenotype, including need for early treatment escalation as a marker of progressive disease using Cox proportional hazards.RESULTS:
In stage 1, each leukocyte subset [CD4+ and CD8+ T-cells and CD14+ monocytes] was analysed in IBD and controls. Three specific miRNAs differentiated IBD from controls in CD4+ T-cells, including miR-1307-3p [pâ =â 0.01], miR-3615 [pâ =â 0.02] and miR-4792 [pâ =â 0.01]. In the extension cohort, in stage 2, miR-1307-3p was able to predict disease progression in IBD (hazard ratio [HR] 1.98, interquartile range [IQR] 1.20-3.27; logrank pâ =â 1.80â ×â 10-3), in particular CD [HR 2.81; IQR 1.11-3.53, pâ =â 6.50â ×â 10-4]. Using blood-based multimarker miRNA models, the estimated chance of escalation in CD was 83% if two or more criteria were met and 90% for UC if three or more criteria are met.INTERPRETATION:
We have identified and validated unique CD4+ T-cell miRNAs that are differentially regulated in IBD. These miRNAs may be able to predict treatment escalation and have the potential for clinical translation; further prospective evaluation is now indicated.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
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Doenças Inflamatórias Intestinais
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MicroRNAs
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Imagem Corporal Total
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article