Donor-specific circulating cell free DNA as a noninvasive biomarker of graft injury in heart transplantation
- Resource Type
- Authors
- Alejandro Adsuar-Gómez; Ángel Herruzo-Avilés; Manuel Porras-López; J. A. Noval-Padillo; Noelia García-Fernández; Patrocinio Molinero; Juan M. Guerrero; Antonio González-Calle; Hada C. Macher; José Miguel Borrego-Domínguez; Amalia Rubio
- Source
- Digital.CSIC. Repositorio Institucional del CSIC
instname
- Subject
- 0301 basic medicine
Adult
Male
medicine.medical_specialty
medicine.medical_treatment
Clinical Biochemistry
Hearth transplantation
Urology
Context (language use)
Biochemistry
Polymerase Chain Reaction
03 medical and health sciences
Basal (phylogenetics)
Cell-free DNA
0302 clinical medicine
Biopsy
Medicine
Humans
Digital polymerase chain reaction
Aged
Heart transplantation
medicine.diagnostic_test
business.industry
Biochemistry (medical)
General Medicine
Immunotherapy
Middle Aged
Circulating Cell-Free DNA
Tissue Donors
Transplantation
030104 developmental biology
030220 oncology & carcinogenesis
Graft rejection
Heart Transplantation
Patient Compliance
Female
business
Cell-Free Nucleic Acids
Biomarkers
- Language
[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.
This work was supported by a grant from the Instituto de Salud Carlos III [FIS: PI15/00939]-Fondos FEDER.