Estefanía Tarazón1, Ana Ortega1, Carolina Gil-Cayuela1, Elena Sánchez-Lacuesta2, Pilar Marín3, Francisca Lago4, José Ramón González-Juanatey4, Luis Martínez-Dolz5, Manuel Portolés1, Miguel Rivera1, Esther Roselló-Lletí6. 1. Cardiocirculatory Unit, Health Research Institute Hospital La Fe, Valencia, Spain and CIBERCV. 2. Hemodynamic Unit, Cardiology Department, University and Polytechnic La Fe Hospital, Valencia, Spain. 3. Microscopy Unit, Health Research Institute Hospital La Fe, Valencia, Spain. 4. Cellular and Molecular Cardiology Research Unit, Department of Cardiology and Institute of Biomedical Research, University Clinical Hospital, Santiago de Compostela, Spain and CIBERCV. 5. Heart Failure and Transplantation Unit, Cardiology Department, University and Polytechnic La Fe Hospital, Valencia, Spain and CIBERCV. 6. Cardiocirculatory Unit, Health Research Institute Hospital La Fe, Valencia, Spain and CIBERCV. Electronic address: esther_rosello_lleti@hotmail.com.
Abstract
BACKGROUND: The detection of heart transplant rejection by non-invasive methods remains a major challenge. Despite the well-known importance of the study of sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) in the heart, its role as a rejection marker has never been analyzed. Our objective in this study was to determine whether circulating SERCA2a could be a good marker of cardiac rejection. METHODS: We collected 127 consecutive endomyocardial biopsies (EMBs) and serum samples from adult heart transplant recipients (49 without allograft rejection and 78 with the diagnosis of biopsy allograft rejection, including 48 Grade 1R, 21 Grade 2R and 9 Grade 3R). Serum concentrations of SERCA2a were determined using a specific sandwich enzyme-linked immunosorbent assay. We also analyzed SERCA2a expression changes on EMBs using immunofluorescence. RESULTS: SERCA2a cardiac tissue and serum levels were decreased in patients with cardiac rejection (p < 0.0001). A receiver-operating characteristic analysis showed that SERCA2a strongly discriminated between patients with and without allograft rejection: normal grafts vs all rejecting grafts (AUC = 0.804); normal grafts vs Grade 1R (AUC = 0.751); normal grafts vs Grade 2R (AUC = 0.875); normal grafts vs Grade 3R (AUC = 0.922); normal grafts vs Grade 2R and 3R (AUC = 0.889), with p < 0.0001 for all comparisons. CONCLUSIONS: We demonstrated that changes in SERCA2a cardiac tissue and serum levels occur in cardiac allograft rejection. Our findings suggest that SERCA2a concentration assessment may be a relatively simple, non-invasive test for heart transplant rejection, showing a strong capability for detection that improves progressively as rejection grades increase.
BACKGROUND: The detection of heart transplant rejection by non-invasive methods remains a major challenge. Despite the well-known importance of the study of sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) in the heart, its role as a rejection marker has never been analyzed. Our objective in this study was to determine whether circulating SERCA2a could be a good marker of cardiac rejection. METHODS: We collected 127 consecutive endomyocardial biopsies (EMBs) and serum samples from adult heart transplant recipients (49 without allograft rejection and 78 with the diagnosis of biopsy allograft rejection, including 48 Grade 1R, 21 Grade 2R and 9 Grade 3R). Serum concentrations of SERCA2a were determined using a specific sandwich enzyme-linked immunosorbent assay. We also analyzed SERCA2a expression changes on EMBs using immunofluorescence. RESULTS: SERCA2a cardiac tissue and serum levels were decreased in patients with cardiac rejection (p < 0.0001). A receiver-operating characteristic analysis showed that SERCA2a strongly discriminated between patients with and without allograft rejection: normal grafts vs all rejecting grafts (AUC = 0.804); normal grafts vs Grade 1R (AUC = 0.751); normal grafts vs Grade 2R (AUC = 0.875); normal grafts vs Grade 3R (AUC = 0.922); normal grafts vs Grade 2R and 3R (AUC = 0.889), with p < 0.0001 for all comparisons. CONCLUSIONS: We demonstrated that changes in SERCA2a cardiac tissue and serum levels occur in cardiac allograft rejection. Our findings suggest that SERCA2a concentration assessment may be a relatively simple, non-invasive test for heart transplant rejection, showing a strong capability for detection that improves progressively as rejection grades increase.
Authors: Matthew D Zinn; Michael J Wallendorf; Kathleen E Simpson; Ashley D Osborne; James K Kirklin; Charles E Canter Journal: Pediatr Transplant Date: 2018-01-29
Authors: Estefanía Tarazón; Carolina Gil-Cayuela; María García Manzanares; Marta Roca; Francisca Lago; José Ramón González-Juanatey; Elena Sánchez-Lacuesta; Luis Martínez-Dolz; Manuel Portolés; Esther Roselló-Lletí Journal: Sci Rep Date: 2019-09-25 Impact factor: 4.379