Biomaterial Database

Diagnostic value of donor-derived cell-free DNA to predict antibody-mediated rejection in donor-specific antibody-positive renal allograft recipients. 2021

Katharina A Mayer, and Konstantin Doberer, and Amanda Tillgren, and Thierry Viard, and Susanne Haindl, and Sebastian Krivanec, and Roman Reindl-Schwaighofer, and Michael Eder, and Farsad Eskandary, and Silvia Casas, and Markus Wahrmann, and Heinz Regele, and Georg A Böhmig

Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria.

Circulating donor-specific antibodies (DSA) do not necessarily indicate antibody-mediated rejection (ABMR). Here, we evaluated the diagnostic value of donor-derived cell-free DNA (dd-cfDNA) as an add-on to DSA detection. The study included two independent cohorts of DSA+ kidney allograft recipients, 45 subclinical cases identified by cross-sectional antibody screening (cohort 1), and 30 recipients subjected to indication biopsies (cohort 2). About 50% of the DSA+ recipients had ABMR and displayed higher dd-cfDNA levels than DSA+ ABMR- recipients (cohort 1: 1.90% [median; IQR: 0.78-3.90%] vs. 0.52% [0.35-0.72%]; P < 0.001); (cohort 2: 1.20% [0.82-2.50%] vs. 0.59% [0.28-2.05%]; P = 0.086). Receiver operating characteristic (ROC) analysis revealed an area under the curve (AUC) of 0.89 and 0.69 for dd-cfDNA, and 0.88 and 0.77 for DSA mean fluorescence intensity (MFI), respectively. In combined models, adding dd-cfDNA to DSA-MFI or vice versa significantly improved the diagnostic accuracy. Limited diagnostic performance of dd-cfDNA in cohort 2 was related to the frequent finding of other types of graft injury among ABMR- recipients, like T cell-mediated rejection or glomerulonephritis. For dd-cfDNA in relation to injury of any cause an AUC of 0.97 was calculated. Monitoring of dd-cfDNA in DSA+ patients may be a useful tool to detect ABMR and other types of injury.

UI	MeSH Term	Description	Entries
D007518	Isoantibodies	Antibodies from an individual that react with ISOANTIGENS of another individual of the same species.	Alloantibodies
D007668	Kidney	Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.	Kidneys
D003430	Cross-Sectional Studies	Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with LONGITUDINAL STUDIES which are followed over a period of time.	Disease Frequency Surveys,Prevalence Studies,Analysis, Cross-Sectional,Cross Sectional Analysis,Cross-Sectional Survey,Surveys, Disease Frequency,Analyses, Cross Sectional,Analyses, Cross-Sectional,Analysis, Cross Sectional,Cross Sectional Analyses,Cross Sectional Studies,Cross Sectional Survey,Cross-Sectional Analyses,Cross-Sectional Analysis,Cross-Sectional Study,Cross-Sectional Surveys,Disease Frequency Survey,Prevalence Study,Studies, Cross-Sectional,Studies, Prevalence,Study, Cross-Sectional,Study, Prevalence,Survey, Cross-Sectional,Survey, Disease Frequency,Surveys, Cross-Sectional
D006084	Graft Rejection	An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient.	Transplant Rejection,Rejection, Transplant,Transplantation Rejection,Graft Rejections,Rejection, Graft,Rejection, Transplantation,Rejections, Graft,Rejections, Transplant,Rejections, Transplantation,Transplant Rejections,Transplantation Rejections
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000073888	Cell-Free Nucleic Acids	Nucleic acids (DNA or RNA) found circulating in SERUM; PLASMA; or other BODY FLUIDS.	Circulating Cell-Free Nucleic Acid,Circulating Nucleic Acid,Cell-Free DNA,Cell-Free Deoxyribonucleic Acid,Cell-Free Nucleic Acid,Cell-Free RNA,Cell-Free Ribonucleic Acid,Circulating Cell-Free Nucleic Acids,Circulating DNA,Circulating Nucleic Acids,Circulating RNA,cfDNA,cfRNA,cirDNA,cirRNA,Acid, Cell-Free Deoxyribonucleic,Acid, Cell-Free Ribonucleic,Acid, Circulating Nucleic,Acids, Circulating Nucleic,Cell Free DNA,Cell Free Deoxyribonucleic Acid,Cell Free Nucleic Acid,Cell Free Nucleic Acids,Cell Free RNA,Cell Free Ribonucleic Acid,Circulating Cell Free Nucleic Acid,Circulating Cell Free Nucleic Acids,DNA, Cell-Free,DNA, Circulating,Deoxyribonucleic Acid, Cell-Free,Nucleic Acid, Cell-Free,Nucleic Acid, Circulating,Nucleic Acids, Cell-Free,Nucleic Acids, Circulating,RNA, Cell-Free,RNA, Circulating,Ribonucleic Acid, Cell-Free
D000906	Antibodies	Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
D016030	Kidney Transplantation	The transference of a kidney from one human or animal to another.	Grafting, Kidney,Renal Transplantation,Transplantation, Kidney,Transplantation, Renal,Kidney Grafting,Kidney Transplantations,Renal Transplantations,Transplantations, Kidney,Transplantations, Renal
D064591	Allografts	Tissues, cells, or organs transplanted between genetically different individuals of the same species.	Allogeneic Grafts,Allogeneic Transplants,Homografts,Homologous Transplants,Allogeneic Graft,Allogeneic Transplant,Allograft,Graft, Allogeneic,Grafts, Allogeneic,Homograft,Homologous Transplant,Transplant, Allogeneic,Transplant, Homologous,Transplants, Allogeneic,Transplants, Homologous