Date Published: January 26, 2017
Publisher: Public Library of Science
Author(s): Ihdina Sukma Dewi, Zsuzsanna Hollander, Karen K. Lam, Janet-Wilson McManus, Scott J. Tebbutt, Raymond T. Ng, Paul A. Keown, Robert W. McMaster, Bruce M. McManus, Olof Gidlöf, Jenny Öhman, Bernard Mari.
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.
The main goal of post heart transplantation care is to prevent allograft rejection while minimizing the dose of immunosuppressive treatment. Endomyocardial biopsy represents the gold standard for diagnosing and monitoring acute cellular rejections (ACR), but this invasive technique represents a burden and a risk to cardiac transplant patients worldwide. Sampling error, inter-observer variability and potential complications are other clinical concerns associated with this procedure[1–4]. Although some advancement has been made to find the non-invasive diagnostic tools, they are not widely used and do not eliminate the need for endomyocardial biopsy. Identifying non-invasive and reliable biomarkers for early detection of acute cellular rejection is of great importance and has become a major challenge in solid organ transplantation[6,7].
In heart transplantation, there is an unmet need for non-invasive and relevant diagnostic tools to minimize or even eliminate the use of endomyocardial biopsies. In recent years microRNAs have emerged as promising biomarker candidates in the field of solid organ transplantation given that their expression patterns reflecting both physiological and underlying pathological conditions in humans and their involvement in the regulation of both innate and adaptive immunity[13–16]. The highly tissue-specific expression and remarkable stability in serum and other body fluids are other features, which make microRNAs suitable as biomarkers. Despite the high ribonuclease activity in blood, microRNAs found in circulation are protected from degradation by associating with proteins such as Ago2 or encapsulation in extracellular vesicles.