Identification of a Diagnostic Set of Endomyocardial Biopsy microRNAs for Acute Cellular Rejection Diagnostics in Patients after Heart Transplantation Using Next-Generation Sequencing

Acute cellular rejection (ACR) of heart allografts represents the most common reason for graft failure. Endomyocardial biopsies (EMB) are still subject to substantial interobserver variability. Novel biomarkers enabling precise ACR diagnostics may decrease interobserver variability. We aimed to iden...

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Published in:Cells (Basel, Switzerland) Switzerland), 2019-11, Vol.8 (11), p.1400
Main Authors: Nováková, Tereza, Macháčková, Táňa, Novák, Jan, Hude, Petr, Godava, Július, Žampachová, Víta, Oppelt, Jan, Zlámal, Filip, Němec, Petr, Bedáňová, Helena, Slabý, Ondřej, Bienertová-Vašků, Julie, Špinarová, Lenka, Krejčí, Jan
Format: Article
Language:English
Subjects:
acute cellular rejection
Allografts
Biomarkers
Biopsy
Cardiovascular disease
diagnostics
endomyocardial biopsy
Gene expression
Graft rejection
Heart failure
Heart transplantation
Medical records
microrna
MicroRNAs
miRNA
Next-generation sequencing
Older people
Patients
Population
Statistical analysis
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Summary:Acute cellular rejection (ACR) of heart allografts represents the most common reason for graft failure. Endomyocardial biopsies (EMB) are still subject to substantial interobserver variability. Novel biomarkers enabling precise ACR diagnostics may decrease interobserver variability. We aimed to identify a specific subset of microRNAs reflecting the presence of ACR. Monocentric retrospective study. A total of 38 patients with the anamnesis of ACR were identified and for each patient three consecutive samples of EMB (with, prior and after ACR) were collected. Sixteen trios were used for next-generation sequencing (exploratory cohort); the resting 22 trios were used for validation with qRT-PCR (validation cohort). Statistical analysis was performed using R software. The analysis of the exploration cohort provided the total of 11 miRNAs that were altered during ACR, the three of which (miR-144, miR-589 and miR-182) were further validated in the validation cohort. Using the levels of all 11 miRNAs and principal component analysis, an ACR score was created with the specificity of 91% and sensitivity of 68% for detecting the presence of ACR in the EMB sample. We identified a set of microRNAs altered in endomyocardial biopsies during ACR and using their relative levels we created a diagnostic score that can be used for ACR diagnosis.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells8111400