Hada Celicia Macher1, Noelia García-Fernández1, Alejandro Adsuar-Gómez2, Manuel Porras-López3, Antonio González-Calle2, José Noval-Padillo4, Juan Miguel Guerrero5, Patrocinio Molinero6, José Miguel Borrego-Domínguez7, Ángel Herruzo-Avilés3, Amalia Rubio8. 1. Dept. of Clinical Biochemistry, Instituto de Investigaciones Biomédicas de Sevilla, IBIS, University of Seville, HUVR, Junta de Andalucía, CSIC, Seville, Spain. 2. Cardiac Surgery Department, Virgen del Rocio University Hospital, Seville, Spain. 3. Intensive Care Unit, Virgen del Rocio University Hospital, Seville, Spain. 4. Dept. of Clinical Biochemistry, Instituto de Investigaciones Biomédicas de Sevilla, IBIS, University of Seville, HUVR, Junta de Andalucía, CSIC, Seville, Spain. Electronic address: jangle.noval.sspa@juntadeandalucia.es. 5. Dept. of Clinical Biochemistry, Instituto de Investigaciones Biomédicas de Sevilla, IBIS, University of Seville, HUVR, Junta de Andalucía, CSIC, Seville, Spain. Electronic address: guerrero@us.es. 6. Dept. Of Medical Biochemistry and Molecular Biology and Immunology, Instituto de Investigaciones Biomédicas de Sevilla, IBIS, University of Seville, HUVR, Junta de Andalucía, CSIC, Seville, Spain. Electronic address: molinero@us.es. 7. Cardiac Surgery Department, Virgen del Rocio University Hospital, Seville, Spain. Electronic address: jmiguel.borrego.sspa@juntadeandalucia.es. 8. Dept. Of Medical Biochemistry and Molecular Biology and Immunology, Instituto de Investigaciones Biomédicas de Sevilla, IBIS, University of Seville, HUVR, Junta de Andalucía, CSIC, Seville, Spain. Electronic address: amaliarubio@us.es.
Abstract
BACKGROUND: Considerable effort has been exerted to develop noninvasive diagnostic biomarkers that might replace or reduce the need to perform endomyocardial biopsies. In this context, graft DNA circulating on transplant recipients has been proposed as a potential biomarker of organ rejection or cellular graft injury. METHODS: We propose a digital PCR (dPCR) method based on the amplification of ten specific InDels sufficiently sensitive to detect small amounts of specific donor circulating DNA diluted on the host cell free DNA (cfDNA). We obtained 23 informative mismatches from 30 host and donor organ biopsy pairs. RESULTS: Patients without heart-related complications showed a high increase in the specific genomic marker levels during the first 24 h after transplantation that dropped to the basal levels on days 3-4 post-surgery. In contrast, patients with complications presented a significantly lagged decay pattern from day one after transplantation. A specific donor cfDNA increase was detected in one patient two days before rejection diagnosis, diminishing the basal levels after successful immunotherapy. A cfDNA increase was also observed during graft injury due to heart damage. CONCLUSION: These results suggest that cfDNA monitoring of transplanted patients may be a useful tool to detect and probably anticipate graft rejection.
BACKGROUND: Considerable effort has been exerted to develop noninvasive diagnostic biomarkers that might replace or reduce the need to perform endomyocardial biopsies. In this context, graft DNA circulating on transplant recipients has been proposed as a potential biomarker of organ rejection or cellular graft injury. METHODS: We propose a digital PCR (dPCR) method based on the amplification of ten specific InDels sufficiently sensitive to detect small amounts of specific donor circulating DNA diluted on the host cell free DNA (cfDNA). We obtained 23 informative mismatches from 30 host and donor organ biopsy pairs. RESULTS:Patients without heart-related complications showed a high increase in the specific genomic marker levels during the first 24 h after transplantation that dropped to the basal levels on days 3-4 post-surgery. In contrast, patients with complications presented a significantly lagged decay pattern from day one after transplantation. A specific donor cfDNA increase was detected in one patient two days before rejection diagnosis, diminishing the basal levels after successful immunotherapy. A cfDNA increase was also observed during graft injury due to heart damage. CONCLUSION: These results suggest that cfDNA monitoring of transplanted patients may be a useful tool to detect and probably anticipate graft rejection.
Authors: Michael Oellerich; Karen Sherwood; Paul Keown; Ekkehard Schütz; Julia Beck; Johannes Stegbauer; Lars Christian Rump; Philip D Walson Journal: Nat Rev Nephrol Date: 2021-05-24 Impact factor: 28.314
Authors: Hajnalka Andrikovics; Zoltán Őrfi; Nóra Meggyesi; András Bors; Lívia Varga; Petra Kövy; Zsófia Vilimszky; Fanni Kolics; László Gopcsa; Péter Reményi; Attila Tordai Journal: Int J Mol Sci Date: 2019-09-10 Impact factor: 5.923