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

• Published in: PloS one Vol. 12; no. 1; p. e0170842
• Main Authors: Sukma Dewi, Ihdina, Hollander, Zsuzsanna, Lam, Karen K., McManus, Janet-Wilson, Tebbutt, Scott J., Ng, Raymond T., Keown, Paul A., McMaster, Robert W., McManus, Bruce M., Gidlöf, Olof, Öhman, Jenny
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 26.01.2017; Public Library of Science (PLoS)
• Subjects: Adaptor Proteins, Signal Transducing - blood; Adaptor Proteins, Signal Transducing - genetics; Adult; Bioindicators; Biology and life sciences; Biomarkers; Biomarkers - blood; Biopsy; Blood; C-Reactive Protein - metabolism; Calcineurin; Cardiology; Case-Control Studies; Clinical Laboratory Medicine; Clinical Medicine; Creatinine; Creatinine - blood; Cyclosporine - blood; Development and progression; Diagnostic software; Diagnostic systems; Female; Gene expression; Gene Expression Regulation; Genetic aspects; Graft rejection; Graft Rejection - blood; Graft Rejection - diagnosis; Graft Rejection - immunology; Graft Rejection - pathology; Heart; Heart Transplantation; Hospitals; Humans; Klinisk laboratoriemedicin; Klinisk medicin; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Medicine and Health Sciences; MicroRNA; MicroRNAs; MicroRNAs - blood; MicroRNAs - genetics; Middle Aged; miRNA; Pathology; Patients; Physiological aspects; Prevention; Rejection; Research and Analysis Methods; Serum levels; Signal Transduction; Tacrolimus; Tacrolimus - blood; Transplantation; Transplants & implants; Canada
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0170842

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. 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. 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. 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.