Biomarkers of Acute Rejection Following Cardiac Transplantation

Abstract

Cardiac transplantation can be a life-saving treatment for selected patients with heart failure. However, despite advances in immunosuppressive therapy, acute allograft rejection remains a significant cause of morbidity and mortality. The current 'gold standard' for rejection surveillance is endomyocardial biopsy, which aims to identify episodes of rejection prior to development of clinical manifestations. This is an invasive technique with a risk of false-positive and false-negative results. Consequently, a wide variety of noninvasive alternatives have been investigated for their potential role as biomarkers of rejection. This article reviews the evidence behind proposed alternatives such as imaging techniques, electrophysiological parameters and peripheral blood markers, and highlights the potential future role for biomarkers in cardiac transplantation as an adjunct to biopsy.

SERCA2a: A potential non-invasive biomarker of cardiac allograft rejection

“…To date, imaging techniques have not shown sufficient diagnostic accuracy to serve as a non-invasive alternative to biopsies. 6,22 Acute rejection has been associated with high levels of circulating BNP 23,24 and NT-proBNP. 25,26 However, other evidence has shown that serial changes in BNP and NT-proBNP represent better predictors of acute rejection than absolute values, 27,28 and these changes found in peripheral blood are not tested in allograft biopsies.…”

“…However, the results obtained in those studies are contradictory and most of them showed low positive predictive values or additional substantial costs associated with management of heart transplant recipients. [3][4][5][6] Much of the experimental evidence has indicated that the enzyme responsible for reloading the sarcoplasmic reticulum with calcium during relaxation, the sarcoplasmic reticulum Ca 2þ -ATPase (SERCA2a), plays a major role in regulating the progression of heart failure by contributing directly to impaired cardiac contraction and relaxation. 7,8 SERCA2a is decreased in cardiac tissue isolated from failing hearts, and this decrease correlates with high diastolic levels of cytosolic calcium and low systolic calcium released from the sarcoplasmic reticulum.…”

Comparative analysis of diagnostic significance of biomarkers’ panels in cardiac recipients in the long term period after transplantation

“…Однако сложность их применения на практике обус-лавливается неспецифичностью тестов и наличием большого числа факторов, влияющих на уровень этих показателей [7][8][9][10][11][12]. Использование панели из нескольких аналитов позволяет повысить чувс-твительность и специфичность мультимаркерных тестов [13,14].…”

An Algorithm Measuring Donor Cell-Free DNA in Plasma of Cellular and Solid Organ Transplant Recipients That Does Not Require Donor or Recipient Genotyping

“…However, this approach has significant limitations including the logistics of organizing the biopsy at short notice and risks associated with an invasive procedure. Non-invasive tests are safer and allow for more frequent monitoring, but current tests are generally too non-specific or insensitive for reliable rejection monitoring ( 1 ).…”