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Cell free DNA rejection

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https://www.readbyqxmd.com/read/28624139/applying-rigor-and-reproducibility-standards-to-assay-donor-derived-cell-free-dna-as-a-non-invasive-method-for-detection-of-acute-rejection-and-graft-injury-after-heart-transplantation
#1
Sean Agbor-Enoh, Ilker Tunc, Iwijn De Vlaminck, Ulgen Fideli, Andrew Davis, Karen Cuttin, Kenneth Bhatti, Argit Marishta, Michael A Solomon, Annette Jackson, Grace Graninger, Bonnie Harper, Helen Luikart, Jennifer Wylie, Xujing Wang, Gerald Berry, Charles Marboe, Kiran Khush, Jun Zhu, Hannah Valantine
BACKGROUND: Use of new genomic techniques in clinical settings requires that such methods are rigorous and reproducible. Previous studies have shown that quantitation of donor-derived cell-free DNA (%ddcfDNA) by unbiased shotgun sequencing is a sensitive, non-invasive marker of acute rejection after heart transplantation. The primary goal of this study was to assess the reproducibility of %ddcfDNA measurements across technical replicates, manual vs automated platforms, and rejection phenotypes in distinct patient cohorts...
May 20, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28441386/graft-derived-cell-free-dna-a-noninvasive-early-rejection-and-graft-damage-marker-in-liver-transplantation-a-prospective-observational-multicenter-cohort-study
#2
MULTICENTER STUDY
Ekkehard Schütz, Anna Fischer, Julia Beck, Markus Harden, Martina Koch, Tilo Wuensch, Martin Stockmann, Björn Nashan, Otto Kollmar, Johannes Matthaei, Philipp Kanzow, Philip D Walson, Jürgen Brockmöller, Michael Oellerich
BACKGROUND: Graft-derived cell-free DNA (GcfDNA), which is released into the blood stream by necrotic and apoptotic cells, is a promising noninvasive organ integrity biomarker. In liver transplantation (LTx), neither conventional liver function tests (LTFs) nor immunosuppressive drug monitoring are very effective for rejection monitoring. We therefore hypothesized that the quantitative measurement of donor-derived cell-free DNA (cfDNA) would have independent value for the assessment of graft integrity, including damage from acute rejection...
April 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28416944/evaluation-of-digital-pcr-as-a-technique-for-monitoring-acute-rejection-in-kidney-transplantation
#3
Hyeseon Lee, Young-Mi Park, Yu-Mee We, Duck Jong Han, Jung-Woo Seo, Haena Moon, Yu-Ho Lee, Yang-Gyun Kim, Ju-Young Moon, Sang-Ho Lee, Jong-Keuk Lee
Early detection and proper management of kidney rejection are crucial for the long-term health of a transplant recipient. Recipients are normally monitored by serum creatinine measurement and sometimes with graft biopsies. Donor-derived cell-free deoxyribonucleic acid (cfDNA) in the recipient's plasma and/or urine may be a better indicator of acute rejection. We evaluated digital PCR (dPCR) as a system for monitoring graft status using single nucleotide polymorphism (SNP)-based detection of donor DNA in plasma or urine...
March 2017: Genomics & Informatics
https://www.readbyqxmd.com/read/28339927/characterizing-the-early-inflammatory-contribution-of-the-donor-kidney-following-reperfusion
#4
John P Stone, Muna Mohamud, Kavit Amin, William R Critchley, Rebecca J Edge, Marc J Clancy, Alexandra L Ball, James E Fildes
Background.: Donor kidneys contain a large reservoir of passenger leucocytes that contribute to acute rejection via direct alloantigen presentation and pro-inflammatory cytokine secretion. However, the early contribution of these cells following revascularization has not previously been described. We performed a secondary, high-volume preservation flush following cold storage to characterize the inflammatory contribution of the donor kidney upon reperfusion. Methods.: Porcine kidneys were retrieved using a protocol analogous to current UK clinical practice...
February 27, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28317398/cardiac-transplantation-towards-a-new-noninvasive-approach-of-cardiac-allograft-rejection
#5
REVIEW
Sophie I Mavrogeni, George Athanasopoulos, Aggeliki Gouziouta, Evangelos Leontiadis, Stamatis Adamopoulos, Genovefa Kolovou
Cardiac allograft rejection (CAR) may occur after transplantation and remains silent, until hemodynamic deterioration takes place. Endomyocardial biopsy (EMB) is applied to early detect CAR. Although, flexible bioptoms have decreased the incidence of lethal complications, EMB remains an invasive procedure carrying risk of tamponade and permanent heart block. Therefore, a new non-invasive approach is needed. Areas covered: AlloMap molecular expression testing and graft-derived cell-free DNA (GcfDNA) test can be used as blood indices of acute and chronic CAR, respectively...
April 2017: Expert Review of Cardiovascular Therapy
https://www.readbyqxmd.com/read/28306671/noninvasive-monitoring-of-acute-and-chronic-rejection-in-heart-transplantation
#6
Maria G Crespo-Leiro, Gonzalo Barge-Caballero, David Couto-Mallon
PURPOSE OF REVIEW: Recent years have seen advances in the early detection of cardiac graft rejection. RECENT FINDINGS: We review the possibilities offered by tissue Doppler imaging and speckle tracking echocardiography, cardiac magnetic resonance, cardiac computed tomography, single positron emission tomography, gene expression profiling, and quantitation of donor-derived cell-free DNA, and microRNAs. SUMMARY: Noninvasive monitoring of acute and chronic rejection after cardiac transplantation is an unmet need and remains a challenge...
March 16, 2017: Current Opinion in Cardiology
https://www.readbyqxmd.com/read/28301387/antibody-mediated-rejection-in-heart-transplantation-new-developments-and-old-uncertainties
#7
Valentina Manfredini, Ornella Leone, Valentina Agostini, Luciano Potena
PURPOSE OF REVIEW: Antibody-mediated rejection (AMR) currently represents one of the main problems for clinical management of heart transplant because of its diagnostic complexity and poor evidences supporting treatments. RECENT FINDINGS: Disorder-based diagnosis is a cornerstone in defining AMR. The limitations of the current classification have been partially overcome by novel studies improving the description of the immune-pathological graft abnormalities, and by new molecular approaches allowing a better understanding of the mechanisms behind AMR and of its relationship with cellular rejection and chronic vasculopathy...
June 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28267558/rapid-detection-of-donor-cell-free-dna-in-lung-transplant-recipients-with-rejections-using-donor-recipient-hla-mismatch
#8
Jun Zou, Brian Duffy, Michael Slade, Andrew Lee Young, Nancy Steward, Ramsey Hachem, T Mohanakumar
Fiberoptic bronchoscopy and transbronchial lung biopsy are currently the gold standard for detection of acute rejection following human lung transplantation (LTx). However, these surveillance procedures are expensive and invasive. Up to now, there are few new methods that have demonstrated clinical utility for detecting early stages of rejection following human lung transplantation. We optimized and technically validated a novel method to quantify donor-derived circulating cell free DNA (DcfDNA) that can be used as an early biomarker for lung allograft rejection...
April 2017: Human Immunology
https://www.readbyqxmd.com/read/28100495/probe-free-digital-pcr-quantitative-methodology-to-measure-donor-specific-cell-free-dna-after-solid-organ-transplantation
#9
Su Kah Goh, Vijayaragavan Muralidharan, Christopher Christophi, Hongdo Do, Alexander Dobrovic
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)...
March 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/27981672/performance-of-the-neobona-test-a-new-paired-end-massively-parallel-shotgun-sequencing-approach-for-cell-free-dna-based-aneuploidy-screening
#10
V Cirigliano, E Ordoñez, L Rueda, A Syngelaki, K H Nicolaides
OBJECTIVE: To assess the performance of screening for fetal trisomies 21, 18 and 13 by cell-free (cf) DNA analysis of maternal blood using a new method based on paired-end massively parallel shotgun sequencing (MPSS). METHODS: This was a blinded study of plasma samples (1mL) obtained from 1000 women undergoing screening for fetal trisomies 21, 18 and 13 at 11-13 weeks' gestation. The study included 50 cases with confirmed fetal trisomy 21, 30 with trisomy 18, 10 with trisomy 13 and 910 unaffected pregnancies...
April 2017: Ultrasound in Obstetrics & Gynecology
https://www.readbyqxmd.com/read/27861289/the-effect-of-asp2409-a-novel-cd86-selective-variant-of-ctla4-ig-on-renal-allograft-rejection-in-nonhuman-primates
#11
Shinsuke Oshima, Erik E Karrer, Yuka Kawato, Masashi Maeda, Hidehiko Fukahori, Susumu Tsujimoto, Jun Hirose, Koji Nakamura, Takanori Marui, Fujiko Takamura, Takahisa Noto, Steven J Chapin, Yasutomo Fujii, Margaret Neighbors, Sridhar Viswanathan, Bruce H Devens, Yasuyuki Higashi
BACKGROUND: Blockade of CD28-mediated T cell costimulation by a modified cytotoxic T lymphocyte-associated antigen 4 (CTLA4-Ig), belatacept, is a clinically effective immunosuppressive therapy for the prevention of renal allograft rejection. Use of belatacept-based calcineurin inhibitor-free immunosuppression, however, has demonstrated an increased frequency of cellular rejection episodes and immunosuppression-related safety issues relative to conventional regimens. Furthermore, belatacept typically requires infusion for its administration chronically, which may present an inconvenience to patients...
December 2016: Transplantation
https://www.readbyqxmd.com/read/27727019/validation-of-a-clinical-grade-assay-to-measure-donor-derived-cell-free-dna-in-solid-organ-transplant-recipients
#12
Marica Grskovic, David J Hiller, Lane A Eubank, John J Sninsky, Cindy Christopherson, John P Collins, Kathryn Thompson, Mindy Song, Yue S Wang, David Ross, Mitchell J Nelles, James P Yee, Judith C Wilber, Maria G Crespo-Leiro, Susan L Scott, Robert N Woodward
The use of circulating cell-free DNA (cfDNA) as a biomarker in transplant recipients offers advantages over invasive tissue biopsy as a quantitative measure for detection of transplant rejection and immunosuppression optimization. However, the fraction of donor-derived cfDNA (dd-cfDNA) in transplant recipient plasma is low and challenging to quantify. Previously reported methods to measure dd-cfDNA require donor and recipient genotyping, which is impractical in clinical settings and adds cost. We developed a targeted next-generation sequencing assay that uses 266 single-nucleotide polymorphisms to accurately quantify dd-cfDNA in transplant recipients without separate genotyping...
November 2016: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/27713880/an-algorithm-measuring-donor-cell-free-dna-in-plasma-of-cellular-and-solid-organ-transplant-recipients-that-does-not-require-donor-or-recipient-genotyping
#13
Paul M K Gordon, Aneal Khan, Umair Sajid, Nicholas Chang, Varun Suresh, Leo Dimnik, Ryan E Lamont, Jillian S Parboosingh, Steven R Martin, Richard T Pon, Jene Weatherhead, Shelly Wegener, Debra Isaac, Steven C Greenway
Cell-free DNA (cfDNA) has significant potential in the diagnosis and monitoring of clinical conditions. However, accurately and easily distinguishing the relative proportion of DNA molecules in a mixture derived from two different sources (i.e., donor and recipient tissues after transplantation) is challenging. In human cellular transplantation, there is currently no useable method to detect in vivo engraftment, and blood-based non-invasive tests for allograft rejection in solid organ transplantation are either non-specific or absent...
2016: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/27610605/efficient-production-of-biallelic-ggta1-knockout-pigs-by-cytoplasmic-microinjection-of-crispr-cas9-into-zygotes
#14
Bjoern Petersen, Antje Frenzel, Andrea Lucas-Hahn, Doris Herrmann, Petra Hassel, Sabine Klein, Maren Ziegler, Klaus-Gerd Hadeler, Heiner Niemann
BACKGROUND: Xenotransplantation is considered to be a promising solution to the growing demand for suitable donor organs for transplantation. Despite tremendous progress in the generation of pigs with multiple genetic modifications thought to be necessary to overcoming the severe rejection responses after pig-to-non-human primate xenotransplantation, the production of knockout pigs by somatic cell nuclear transfer (SCNT) is still an inefficient process. Producing genetically modified pigs by intracytoplasmic microinjection of porcine zygotes is an alluring alternative...
September 2016: Xenotransplantation
https://www.readbyqxmd.com/read/26976360/de-novo-proliferative-glomerulonephritis-with-monoclonal-igg-deposits-of-the-igg1%C3%AE%C2%BA-subtype-in-a-kidney-allograft
#15
Takahiro Tsuji, Masayoshi Miura, Mitsuru Yanai, Hiroe Itami, Yasushi Ishii, Mayuko Akimoto, Yuichiro Fukasawa
Proliferative glomerulonephritis with monoclonal immunoglobulin G (IgG) deposits (PGNMID) has recently been described in cases with glomerular disease. Only 16 cases of recurrent or de novo PGNMID have been reported in the transplanted kidney. Here we report a case of de novo PGNMID in a renal allograft diagnosed in the early stage by protocol biopsy. A 41-year-old male with end-stage kidney disease caused by focal glomerular sclerosis received a living-related kidney transplant. The post-transplantation course was stable, except for an early episode of acute T cell-mediated rejection...
July 2016: Nephrology
https://www.readbyqxmd.com/read/26574891/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
#16
COMPARATIVE STUDY
Martina Adamek, Gerhard Opelz, Katrin Klein, Christian Morath, Thuong Hien Tran
BACKGROUND: Timely 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...
July 1, 2016: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/26518940/donor-derived-cell-free-dna-is-a-novel-universal-biomarker-for-allograft-rejection-in-solid-organ-transplantation
#17
J Beck, M Oellerich, U Schulz, V Schauerte, L Reinhard, U Fuchs, C Knabbe, A Zittermann, C Olbricht, J F Gummert, M Shipkova, I Birschmann, E Wieland, E Schütz
BACKGROUND: In solid organ transplantation, sensitive real-time biomarkers to assess the graft health are desirable to enable early intervention, for example, to avoid full-blown rejections. During rejection, high amounts of graft-derived cell-free DNA (GcfDNA) are shed into the blood stream. The quantification of this GcfDNA in allotransplantation is considered to fulfill this need, because it can be measured with great precision and at reasonable cost. PATIENTS AND METHODS: Patients from 2 ongoing studies in kidney (KTx) and heart (HTx) transplantation were monitored blinded on a scheduled basis, by means of a published universal droplet digital polymerase chain reaction to quantify the GcfDNA...
October 2015: Transplantation Proceedings
https://www.readbyqxmd.com/read/26466143/monitoring-pharmacologically-induced-immunosuppression-by-immune-repertoire-sequencing-to-detect-acute-allograft-rejection-in-heart-transplant-patients-a-proof-of-concept-diagnostic-accuracy-study
#18
Christopher Vollmers, Iwijn De Vlaminck, Hannah A Valantine, Lolita Penland, Helen Luikart, Calvin Strehl, Garrett Cohen, Kiran K Khush, Stephen R Quake
BACKGROUND: It remains difficult to predict and to measure the efficacy of pharmacological immunosuppression. We hypothesized that measuring the B-cell repertoire would enable assessment of the overall level of immunosuppression after heart transplantation. METHODS AND FINDINGS: In this proof-of-concept study, we implemented a molecular-barcode-based immune repertoire sequencing assay that sensitively and accurately measures the isotype and clonal composition of the circulating B cell repertoire...
October 2015: PLoS Medicine
https://www.readbyqxmd.com/read/26460048/noninvasive-monitoring-of-infection-and-rejection-after-lung-transplantation
#19
Iwijn De Vlaminck, Lance Martin, Michael Kertesz, Kapil Patel, Mark Kowarsky, Calvin Strehl, Garrett Cohen, Helen Luikart, Norma F Neff, Jennifer Okamoto, Mark R Nicolls, David Cornfield, David Weill, Hannah Valantine, Kiran K Khush, Stephen R Quake
The survival rate following lung transplantation is among the lowest of all solid-organ transplants, and current diagnostic tests often fail to distinguish between infection and rejection, the two primary posttransplant clinical complications. We describe a diagnostic assay that simultaneously monitors for rejection and infection in lung transplant recipients by sequencing of cell-free DNA (cfDNA) in plasma. We determined that the levels of donor-derived cfDNA directly correlate with the results of invasive tests of rejection (area under the curve 0...
October 27, 2015: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/26418703/graft-derived-cell-free-dna-as-a-marker-of-transplant-graft-injury
#20
REVIEW
Michael Oellerich, Philip D Walson, Julia Beck, Jessica Schmitz, Otto Kollmar, Ekkehard Schütz
Although short-term success after solid organ transplantation is good, long-term graft and recipient survival are both not satisfactory. Despite therapeutic drug monitoring (TDM) of immunosuppressive drugs (ISDs), both excessive and insufficient immunosuppression still do occur. There is a need for new biomarkers that, when combined with TDM, can be used to provide more effective and less toxic, personalized immunosuppression to improve long-term survival. Currently used methods are insufficient to rapidly, cost-effectively, and directly interrogate graft integrity after solid organ transplantation...
April 2016: Therapeutic Drug Monitoring
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