Novel Biomarker Approaches for Managing Patients With Cardiac Transplantation

Abstract

Despite major advances in the medical care of patients following heart transplantation (HTx) and a steady increase in long-term survival, allograft surveillance is still based on endomyocardial biopsy, the gold standard since the 1970s. This invasive procedure calls for less burdening and more cost-effective approaches. In recent years, impressive progress has been made in utilizing blood-based biomarkers for the diagnosis and management of diseases in a variety of fields. Hence, a number of trials have been performed testing the usefulness of circulating molecules or other technical methods to overcome the need for surveillance myocardial biopsy in HTx patients. Here, we review current approaches and the state of research on novel biomarkers for the management of patients following heart transplantation.

Heart Transplant: Protocol for Monitoring Posttransplant Complications

“…Despite the development of a variety of non-invasive methods for the detection of rejection, the endomyocardial biopsy will remain important in the management of patients following cardiac transplantation, as non-invasive techniques are associated with low specificity for the diagnosis of rejection [18][19][20][21][22]. Some biomarkers associated with the early immune response to cardiac allograft retain the power to be diagnostic and, even better, predictive of acute rejection, as in the case of pretransplant CXCL10 serum level, but still multicenter studies are needed for validation and standardization of such biomarkers in daily clinical practice [23].…”

Osteopontin and Transplantation: Where Are We Now?

“…Despite the progress in donor–recipient matching, and modern immunosuppression, graft rejection is still a leading cause of death after HTx. The most common cause of late graft failure is cardiac allograft vasculopathy (CAV) (Kennel and Schulze 2015 ). Endomyocardial biopsy (EMB) is the standard method for early detection of acute cellular rejection; however, EMB is more relevant to CAV prognosis than diagnosis, because it has low sensitivity due to the exclusion of microvasculature (Hiemann et al 2007 ).…”

“…Endomyocardial biopsy (EMB) is the standard method for early detection of acute cellular rejection; however, EMB is more relevant to CAV prognosis than diagnosis, because it has low sensitivity due to the exclusion of microvasculature (Hiemann et al 2007 ). Therefore, a lot of research is carried out to establish precise biomarkers in cardiac biopsy tissue as well as in blood which can be used for graft rejection screening (Kennel and Schulze 2015 ). Considering the role of OPN in various cardiovascular pathologies, as well as inflammatory conditions, it has been proposed that this protein may be implicated in HTx outcomes.…”

Clinical potential of DNA methylation in organ transplantation

“…Allomap, a commercially available blood-based test to diagnose cardiac allograft rejection, is based on gene expression levels of 11 genes. 7 It was developed based on results of the Invasive Monitoring Attenuation through Gene Expression (IMAGE) 8 and CARGO trials. 9 In both of those studies gene expression analysis resulted in significantly fewer biopsies taken to monitor the allograft.…”

“…17 Integration of molecular techniques to provide biomarkers for complications after organ transplantation holds potential for improving on currently used diagnostics. 7,11,15 Epigenetic mechanism: DNA methylation There are several epigenetic mechanisms that influence the condensation of chromatin to make specific genes accessible or inaccessible to transcription factors, and thereby determine which genes are transcribed. 18 Histone modifications, such as methylation or acetylation, non-coding RNA molecules that bind the DNA (siRNAs, lncRNAs, micro-RNAs), and methylation of DNA are the main epigenetic mechanisms, 19 which have been nicely illustrated in an extensive review by Portela and Esteller.…”