Association of Serum MiR-142-3p and MiR-101-3p Levels with Acute Cellular Rejection after Heart Transplantation

PLoS One. 2017 Jan 26;12(1):e0170842. doi: 10.1371/journal.pone.0170842. eCollection 2017.

Abstract

Background: Identifying non-invasive and reliable blood-derived biomarkers for early detection of acute cellular rejection in heart transplant recipients is of great importance in clinical practice. MicroRNAs are small molecules found to be stable in serum and their expression patterns reflect both physiological and underlying pathological conditions in human.

Methods: We compared a group of heart transplant recipients with histologically-verified acute cellular rejection (ACR, n = 26) with a control group of heart transplant recipients without allograft rejection (NR, n = 37) by assessing the levels of a select set of microRNAs in serum specimens.

Results: The levels of seven microRNAs, miR-142-3p, miR-101-3p, miR-424-5p, miR-27a-3p, miR-144-3p, miR-339-3p and miR-326 were significantly higher in ACR group compared to the control group and could discriminate between patients with and without allograft rejection. MiR-142-3p and miR-101-3p had the best diagnostic test performance among the microRNAs tested. Serum levels of miR-142-3p and miR-101-3p were independent of calcineurin inhibitor levels, as measured by tacrolimus and cyclosporin; kidney function, as measured by creatinine level, and general inflammation state, as measured by CRP level.

Conclusion: This study demonstrated two microRNAs, miR-142-3p and miR-101-3p, that could be relevant as non-invasive diagnostic tools for identifying heart transplant patients with acute cellular rejection.

Publication types

  • Multicenter Study

MeSH terms

  • Adaptor Proteins, Signal Transducing / blood
  • Adaptor Proteins, Signal Transducing / genetics
  • Adult
  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • Case-Control Studies
  • Creatinine / blood
  • Cyclosporine / blood
  • Female
  • Gene Expression Regulation
  • Graft Rejection / blood*
  • Graft Rejection / diagnosis*
  • Graft Rejection / immunology
  • Graft Rejection / pathology
  • Heart Transplantation*
  • Humans
  • Male
  • MicroRNAs / blood*
  • MicroRNAs / genetics
  • Middle Aged
  • Signal Transduction
  • Tacrolimus / blood

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers
  • CABIN1 protein, human
  • MIRN101 microRNA, human
  • MIRN142 microRNA, human
  • MicroRNAs
  • Cyclosporine
  • C-Reactive Protein
  • Creatinine
  • Tacrolimus

Grants and funding

This study was supported by The Swedish Heart and Lung Foundation (Grant Number: 20130543 to Dr. Jenny Öhman), Skåne University Hospital Funds, and the Foundations of Anna-Lisa and Sven-Eric Lundgren, Kocks, Crafoord, Lars-Erik Gelin, Lars Hierta and Tore Nilsson, respectively. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.