GENETIC BIOMARKERS OF ACUTE GRAFT REJECTION AFTER HEART TRANSPLANTATION

Abstract

Heart transplantation (HT) is the standard of care for end-stage heart failure refractory to medical therapy. Patients after heart transplantation are at risk of developing various complications during their follow-up. Common complications include early allograft failure, acute graft rejection (AGR), coronary allograft vasculopathy (CAV), renal failure, infections, and cancer. Causes for secondary graft dysfunction need to be considered beyond the first week. Nowadays, histological stratification of acute rejection (AR) on endomyocardial biopsy plus histopathology (EMBx) is the standard method for diagnosing acute rejection, assessing its severity, and the response to therapy. Unfortunately, this method is invasive and has some limitations. In addition to that, acute rejection has two phenotypes, acute cellular rejection (ACR) and antibody-mediated rejection (AMR), which challenges the histopathologic diagnosis. Secondary non-genetic methods for monitoring cardiac rejection may include echocardiography, cardiac MRI, troponin, and other methods. A reliable non-invasive marker to detect acute rejection prior to the development of graft dysfunction would possibly result in better outcomes for those patients who develop allograft rejection. In the current review, we collect recent data about genetic non-invasive biomarkers including donor derived cell free DNA, DNA-methylation, RNAs Gene expression profiling (messenger RNA) and micro-RNA. cfDNA methylation analysis can help to distinguish different types of acute rejection. The fraction of cfDNA from the donor decreases rapidly post-transplantation, and increase only in case of acute rejection or myocardial injury. In summary, genetic non-invasive methods have a pivotal role in the assessing and monitoring cardiac allograft rejection. Review article established that DNA-based non-invasive tools minimize the risks of invasive procedures. It is a safe, convenient, and precise method for diagnosing heart failure after cardiac transplantation.