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Platelets. 2020;31(2):198-205. doi: 10.1080/09537104.2019.1585527. Epub 2019 Mar 18.

Circulating microRNAs in patients with immune thrombocytopenia before and after treatment with thrombopoietin-receptor agonists.

Author information

1
Multidisciplinary Laboratory Medicine and Medical Biochemistry, Akershus University Hospital, Lørenskog, Norway.
2
Center for Laboratory Medicine, Østfold Hospital Trust, Grålum, Norway.
3
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
4
Department of Research, Østfold Hospital Trust, Grålum, Norway.
5
Department of Medicine, Østfold Hospital Trust, Grålum, Norway.
6
Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Arrixaca, Servicio de Hematología y Oncología Médica, Murcia, Spain.
7
Grupo de investigación CB15/00055 del Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
8
Department of Pediatrics, Division of Hematology, New York Presbyterian Hospital, Weill Cornell Medicine, New York, NY, USA.
9
Department of Haematology, Oslo University Hospital, Oslo, Norway.
10
Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway.
11
Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, Norway.

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs involved in the regulation of gene expression. Dysregulated expression of several miRNAs has been found in primary immune thrombocytopenia (ITP) suggesting that miRNAs are likely involved in the pathogenesis of ITP. We aimed to explore the differential expression of miRNAs in patients with ITP before and after starting treatment with thrombopoietin-receptor agonists (TPO-RAs) to clarify their roles in the pathophysiology of ITP, and as potential diagnostic and prognostic markers of this disorder.We performed a profiling study where 179 miRNAs were analyzed in eight ITP patients before and during treatment with TPO-RAs and in eight controls using miRNA PCR panel; 81 miRNAs were differentially expressed in ITP patients compared to controls, and 14 miRNAs showed significant changes during TPO-RA-treatment. Ten miRNAs were selected for validation that was performed in 23 patients and 22 controls using droplet digital PCR. Three miRNAs were found to be differentially expressed in ITP patients before TPO-RA-treatment compared to controls: miR-199a-5p was down-regulated (p = 0.0001), miR-33a-5p (p = 0.0002) and miR-195-5p (p = 0.035) were up-regulated. Treatment with TPO-RAs resulted in changes in six miRNAs including miR-199a-5p (p = 0.001), miR-33a-5p (p = 0.003), miR-382-5p (p = 0.004), miR-92b-3p (p = 0.005), miR-26a-5p (p = 0.008) and miR-221-3p (p = 0.023); while miR-195-5p remained unchanged and significantly higher than in controls, despite the increase in the platelet count, which may indicate its possible role in the pathophysiology of ITP. Regression analysis revealed that pre-treatment levels of miR-199a-5p and miR-221-3p could help to predict platelet response to TPO-RA-treatment. ROC curve analysis showed that the combination of miR-199a-5p and miR-33a-5p could distinguish patients with ITP from controls with AUC of 0.93.This study identifies a number of differentially expressed miRNAs in ITP patients before and after initiation of TPO-RAs with potential roles in the pathophysiology, as well as with a possible utility as diagnostic and prognostic biomarkers. These interesting findings deserve further exploration and validation in future studies.

KEYWORDS:

ITP; TPO-RAs; microRNAs

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