Donor-Derived Cell-Free DNA Is a Novel Universal Biomarker for Allograft Rejection in Solid Organ Transplantation

2015 ◽  
Vol 47 (8) ◽  
pp. 2400-2403 ◽  
Author(s):  
J. Beck ◽  
M. Oellerich ◽  
U. Schulz ◽  
V. Schauerte ◽  
L. Reinhard ◽  
...  
Keyword(s):  
Organ Transplantation ◽  
Allograft Rejection ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Cell Free Dna ◽  
Free Dna

scholarly journals Donor-Derived Cell-Free DNA in Kidney Transplantation: Origins, Present and a Look to the Future

Medicina ◽  
2021 ◽  
Vol 57 (5) ◽  
pp. 482
Author(s):  
Sam Kant ◽  
Daniel C. Brennan
Keyword(s):  
Kidney Transplantation ◽  
Organ Transplantation ◽  
Allograft Rejection ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Future Prospects ◽  
Cell Free Dna ◽  
Medical Specialties ◽  
Free Dna ◽  
The Future

Since its first detection in 1948, donor-derived cell-free DNA (dd-cfDNA) has been employed for a myriad of indications in various medical specialties. It has had a far-reaching impact in solid organ transplantation, with the most widespread utilization in kidney transplantation for the surveillance and detection of allograft rejection. The purpose of this review is to track the arc of this revolutionary test—from origins to current use—along with examining challenges and future prospects though the lens of transplant nephrology.

scholarly journals Origin of Plasma Cell-free DNA after Solid Organ Transplantation

2003 ◽  
Vol 49 (3) ◽  
pp. 495-496 ◽  
Author(s):  
Yanni Y N Lui ◽  
Kam-Sang Woo ◽  
Angela Y M Wang ◽  
Chung-Kwong Yeung ◽  
Philip K T Li ◽  
...  
Keyword(s):  
Organ Transplantation ◽  
Plasma Cell ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Cell Free Dna ◽  
Free Dna

Donor-Derived Cell-Free DNA Testing in Solid Organ Transplantation: A Value Proposition

2020 ◽  
Vol 5 (5) ◽  
pp. 993-1004 ◽  
Author(s):  
Michael Oellerich ◽  
Robert H Christenson ◽  
Julia Beck ◽  
Ekkehard Schütz ◽  
Karen Sherwood ◽  
...  
Keyword(s):  
Organ Transplantation ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Value Proposition ◽  
Cell Free Dna ◽  
Long Term Outcome ◽  
Economic Implications ◽  
A Value ◽  
Free Dna ◽  
Protocol Biopsies

Abstract Background There is a need to improve personalized immunosuppression in organ transplantation to reduce premature graft loss. More efficient biomarkers are needed to better detect rejection, asymptomatic graft injury, and under-immunosuppression. Assessment of minimal necessary exposure to guide tapering and to prevent immune activation is also important. Donor-derived cell-free DNA (dd-cfDNA) has become available for comprehensive monitoring of allograft integrity. A value proposition concept was applied to assess the potential benefits of dd-cfDNA to stakeholders (patient, transplant physician, laboratory medicine specialist, hospital management, insurance companies) involved in solid organ transplantation care. Content There is robust clinical evidence from more than 48 published studies supporting the role of dd-cfDNA for monitoring graft integrity and detection or exclusion of rejection. The value proposition framework was used to evaluate published key evidence regarding clinical validity, economic implications, and limitations of this approach. It has been shown that dd-cfDNA testing is essential for guiding earlier transplant injury intervention with potential for improved long-term outcome. Summary Monitoring dd-cfDNA offers a rapid and reproducible method to detect graft injuries at an early actionable stage without protocol biopsies and allows for more effective personalized immunosuppression. The appropriate use of dd-cfDNA testing can provide both clinical and economic benefits to all transplantation stakeholders.

scholarly journals Probe-Free Digital PCR Quantitative Methodology to Measure Donor-Specific Cell-Free DNA after Solid-Organ Transplantation

2017 ◽  
Vol 63 (3) ◽  
pp. 742-750 ◽  
Author(s):  
Su Kah Goh ◽  
Vijayaragavan Muralidharan ◽  
Christopher Christophi ◽  
Hongdo Do ◽  
Alexander Dobrovic
Keyword(s):  
Organ Transplantation ◽  
Graft Rejection ◽  
Solid Organ Transplantation ◽  
Digital Pcr ◽  
Specific Cell ◽  
Solid Organ ◽  
Quantitative Methodology ◽  
Cell Free Dna ◽  
Free Dna ◽  
Specificity And Sensitivity

Abstract BACKGROUND Donor-specific cell-free DNA (dscfDNA) is increasingly being considered as a noninvasive biomarker to monitor graft health and diagnose graft rejection after solid-organ transplantation. However, current approaches used to measure dscfDNA can be costly and/or laborious. A probe-free droplet digital PCR (ddPCR) methodology using small deletion/insertion polymorphisms (DIPs) was developed to circumvent these limitations without compromising the quantification of dscfDNA. This method was called PHABRE-PCR (Primer to Hybridize across an Allelic BREakpoint-PCR). The strategic placement of one primer to hybridize across an allelic breakpoint ensured highly specific PCR amplification, which then enabled the absolute quantification of donor-specific alleles by probe-free ddPCR. METHODS dscfDNA was serially measured in 3 liver transplant recipients. Donor and recipient genomic DNA was first genotyped against a panel of DIPs to identify donor-specific alleles. Alleles that differentiated donor-specific from recipient-specific DNA were then selected to quantify dscfDNA in the recipient plasma. RESULTS Lack of amplification of nontargeted alleles confirmed that PHABRE-PCR was highly specific. In recipients who underwent transplantation, dscfDNA was increased at day 3, but decreased and plateaued at a low concentration by 2 weeks in the 2 recipients who did not develop any complications. In the third transplant recipient, a marked increase of dscfDNA coincided with an episode of graft rejection. CONCLUSIONS PHABRE-PCR was able to quantify dscfDNA with high analytical specificity and sensitivity. The implementation of a DIP-based approach permits surveillance of dscfDNA as a potential measure of graft health after solid-organ transplantation.

Cell-free DNA and RNA - measurement and applications in clinical diagnostics with focus on metabolic disorders

2020 ◽  
Author(s):  
Markus Hodal Drag ◽  
Tuomas Oskari Kilpeläinen
Keyword(s):  
Metabolic Disorders ◽  
Solid Organ Transplantation ◽  
Prenatal Testing ◽  
Clinical Diagnostics ◽  
Solid Organ ◽  
Liquid Biopsies ◽  
Cell Free Dna ◽  
Alcoholic Fatty Liver ◽  
Non Invasive ◽  
Free Dna

Circulating cell-free DNA (cfDNA) and RNA (cfRNA) hold enormous potential as a new class of biomarkers for the development of non-invasive liquid biopsies in many diseases and conditions. In recent years, cfDNA and cfRNA have been studied intensely as tools for non-invasive prenatal testing, solid organ transplantation, cancer screening, and monitoring of tumors. In obesity, higher cfDNA concentration indicates accelerated cellular turnover of adipocytes during expansion of adipose mass and may be directly involved in the development of adipose tissue insulin resistance by inducing inflammation. Furthermore, cfDNA and cfRNA have promising diagnostic value in a range of obesity-related metabolic disorders, such as non-alcoholic fatty liver disease, type 2 diabetes, and diabetic complications. Here, we review the current and future applications of cfDNA and cfRNA within clinical diagnostics, discuss technical and analytical challenges in the field, and summarise the opportunities of using cfDNA and cfRNA in the diagnostics and prognostics of obesity-related metabolic disorders.

scholarly journals Cell-Free DNA in Pediatric Solid Organ Transplantation Using a New Detection Method of Separating Donor-Derived from Recipient Cell-Free DNA

2020 ◽  
Vol 66 (10) ◽  
pp. 1300-1309
Author(s):  
Evgenia Preka ◽  
Drew Ellershaw ◽  
Natalie Chandler ◽  
Helena Ahlfors ◽  
Helen Spencer ◽  
...  
Keyword(s):  
Limit Of Detection ◽  
Low Cost ◽  
Recipient Cell ◽  
Solid Organ Transplantation ◽  
Organ Transplant ◽  
Solid Organ ◽  
Nucleotide Polymorphisms ◽  
Limit Of Quantification ◽  
Cell Free Dna ◽  
Free Dna

Abstract Background The use of cell-free DNA (cfDNA) as a noninvasive biomarker to detect allograft damage is expanding rapidly. However, quantifying the low fraction of donor-derived cfDNA (ddcfDNA) is challenging and requires a highly sensitive technique. ddcfDNA detection through unique donor single nucleotide polymorphisms (SNPs) is a recent new approach, however there are limited data in pediatric solid organ transplant (SOT) recipients. Methods We developed an assay using a combination of 61 SNPs to quantify the ddcfDNA accurately using a custom R script to model for both the patient and donor genotypes requiring only a single sample from the allograft recipient. Performance of the assay was validated using genomic DNA (gDNA), cfDNA and donor samples where available. Results The R “genotype-free” method gave results comparable to when using the known donor genotype. applicable to both related and unrelated pairs and can reliably measure ddcfDNA (limit of blank, below 0.12%; limit of detection, above 0.25%; limit of quantification 0.5% resulting in 84% accuracy). 159 pediatric SOT recipients (kidney, heart, and lung) were tested without the need for donor genotyping. Serial sampling was obtained from 82 patients. Conclusion We have developed and validated a new assay to measure the fraction of ddcfDNA in the plasma of pediatric SOT recipients. Our method can be applicable in any donor-recipient pair without the need for donor genotyping and can provide results in 48 h at a low cost. Additional prospective studies are required to demonstrate its clinical validity in a large cohort of pediatric SOT recipients.

A fast and simple method for detecting and quantifying donor-derived cell-free DNA in sera of solid organ transplant recipients as a biomarker for graft function

2016 ◽  
Vol 54 (7) ◽  
Author(s):  
Martina Adamek ◽  
Gerhard Opelz ◽  
Katrin Klein ◽  
Christian Morath ◽  
Thuong Hien Tran
Keyword(s):  
Graft Rejection ◽  
Graft Function ◽  
Solid Organ Transplantation ◽  
Organ Transplant ◽  
Human Leukocyte ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Simple Method ◽  
Cell Free Dna ◽  
Free Dna

AbstractTimely detection of graft rejection is an important issue in the follow-up care after solid organ transplantation. Until now, biopsy has been considered the “gold standard” in the diagnosis of graft rejection. However, non-invasive tests such as monitoring the levels of cell-free DNA (cfDNA) as a sensitive biomarker for graft integrity have attracted increasing interest. The rationale of this approach is that a rejected organ will lead to a significant release of donor-derived cfDNA, which can be detected in the serum of the transplant recipient.We have developed a novel quantitative real-time PCR (qPCR) approach for detecting an increase of donor-derived cfDNA in the recipient’s serum. Common insertion/deletion (InDel) genetic polymorphisms, which differ between donor and recipient, are targeted in our qPCR assay. In contrast to some other strategies, no specific donor/recipient constellations such as certain gender combinations or human leukocyte antigen (HLA) discrepancies are required for the application of our test.The method was first validated with serial dilutions of serum mixtures obtained from healthy blood donors and then used to determine donor-derived cfDNA levels in patients’ sera within the first 3 days after their kidney transplantation had been performed.Our method represents a universally applicable, simple and cost-effective tool which can potentially be used to detect graft dysfunction in transplant recipients.

The interactive effect of parent personality and medication knowledge on adherence in children awaiting solid organ transplantation.

2017 ◽  
Vol 36 (5) ◽  
pp. 445-448 ◽  
Author(s):  
Jennifer L. Lee ◽  
Cyd K. Eaton ◽  
Kristin Loiselle Rich ◽  
Bonney Reed-Knight ◽  
Rochelle S. Liverman ◽  
...  
Keyword(s):  
Organ Transplantation ◽  
Interactive Effect ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Medication Knowledge ◽  
Parent Personality
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