Schmitz, Jessica E.

[["dc.bibliographiccitation.firstpage","153"],["dc.bibliographiccitation.lastpage","176"],["dc.contributor.author","Oellerich, Michael"],["dc.contributor.author","Beck, Julia"],["dc.contributor.author","Kanzow, Philipp"],["dc.contributor.author","Schmitz, Jessica"],["dc.contributor.author","Kollmar, Otto"],["dc.contributor.author","Walson, Philip D."],["dc.contributor.author","Schütz, Ekkehard"],["dc.contributor.editor","Oellerich, Michael"],["dc.contributor.editor","Dasgupta, Amitava"],["dc.date.accessioned","2020-05-22T06:58:17Z"],["dc.date.available","2020-05-22T06:58:17Z"],["dc.date.issued","2016"],["dc.description.abstract","Genome transplant dynamics is a particularly promising new approach for the detection of graft injury based on the determination of graft-derived circulating cell-free DNA (cfDNA) in the blood of the recipient. An increase of donor DNA is an early indication of organ damage. A novel potential routine assay for graft-derived circulating cfDNA quantification has been developed using droplet digital polymerase chain reaction for the determination of the donor/recipient circulating cfDNA ratio. This method is very cost-effective and provides results on the same day. Monitoring graft-derived cfDNA has the advantage that it directly interrogates the health of the donor organ, and it allows early detection of transplant injury (“liquid biopsy”). The detection of subclinical rejection would be desirable to allow early intervention. Undiagnosed chronic damage can result in chronic rejection. The determination of graft-derived circulating cfDNA may complement or possibly replace other approaches for post-transplant monitoring, and it may improve the chances of long-term graft survival. This method will be helpful to individualize immunosuppressive regimens. Personalized immunosuppression will in the future shift emphasis from reaction to prevention, which could make immunosuppressive drugs safer and more effective and also reduce the cost of health care."],["dc.identifier.doi","10.1016/B978-0-12-800885-0.00007-2"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/65676"],["dc.language.iso","en"],["dc.publisher","Elsevier"],["dc.publisher.place","San Diego"],["dc.relation.doi","10.1016/C2013-0-19247-1"],["dc.relation.isbn","978-0-12-800885-0"],["dc.relation.ispartof","Personalized Immunosuppression in Transplantation"],["dc.title","Graft-derived cell-free DNA as a marker of graft integrity after transplantation"],["dc.type","book_chapter"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","S75"],["dc.bibliographiccitation.journal","Therapeutic Drug Monitoring"],["dc.bibliographiccitation.lastpage","S79"],["dc.bibliographiccitation.volume","38"],["dc.contributor.author","Oellerich, Michael"],["dc.contributor.author","Walson, Philip D."],["dc.contributor.author","Beck, Julia"],["dc.contributor.author","Schmitz, Jessica"],["dc.contributor.author","Kollmar, Otto"],["dc.contributor.author","Schütz, Ekkehard"],["dc.date.accessioned","2020-12-10T18:19:52Z"],["dc.date.available","2020-12-10T18:19:52Z"],["dc.date.issued","2016"],["dc.description.abstract","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. However, because organ transplants are also genome transplants, measurement of graft-derived circulating cell-free DNA (GcfDNA) has shown promise as a way to improve both graft and recipient outcomes after solid organ transplantation through the early detection of severe graft injury, enabling an early intervention. A newly developed droplet digital polymerase chain reaction (ddPCR) method has advantages over expensive high-throughput sequencing methods to rapidly quantify GcfDNA percentages and absolute amounts. This procedure does not require donor DNA and therefore can be applied to any organ donor/recipient pair. The droplet digital polymerase chain reaction method allows for the early, sensitive, specific, and cost-effective direct assessment of graft integrity and can be used to define individual responses to ISDs including the minimal ISD exposures necessary to prevent rejection. This is especially important in patients undergoing ISD switches due to ISD toxicity, infections, or malignancies. Although prospective, multicenter clinical trials in liver, heart, and kidney transplantation have not been completed, early results suggest that GcfDNA can be combined with TDM to guide changes in immunosuppression to provide more effective, and less toxic treatment. Personalized immunosuppression will shift emphasis in transplantation from reaction to prevention and could improve outcome at lower health care costs."],["dc.identifier.doi","10.1097/FTD.0000000000000239"],["dc.identifier.isi","000377003400009"],["dc.identifier.issn","0163-4356"],["dc.identifier.pmid","26418703"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/75409"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","1536-3694"],["dc.relation.issn","0163-4356"],["dc.title","Graft-Derived Cell-Free DNA as a Marker of Transplant Graft Injury"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1732"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Clinical Chemistry"],["dc.bibliographiccitation.lastpage","1741"],["dc.bibliographiccitation.volume","59"],["dc.contributor.author","Beck, Julia"],["dc.contributor.author","Bierau, Sarah"],["dc.contributor.author","Balzer, Stefan"],["dc.contributor.author","Andag, Reiner"],["dc.contributor.author","Kanzow, Philipp"],["dc.contributor.author","Schmitz, Jessica"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Mörer, Onnen"],["dc.contributor.author","Slotta, Jan E."],["dc.contributor.author","Walson, Philip D."],["dc.contributor.author","Kollmar, Otto"],["dc.contributor.author","Oellerich, Michael"],["dc.contributor.author","Schütz, Ekkehard"],["dc.date.accessioned","2020-05-22T07:07:40Z"],["dc.date.available","2020-05-22T07:07:40Z"],["dc.date.issued","2013"],["dc.description.abstract","BACKGROUND Cell-free DNA (cfDNA) from grafts in the circulation of transplant recipients is a potential biomarker of rejection. Its usefulness was investigated after heart transplantation during the maintenance phase by use of microarrays and massive parallel sequencing of donor and recipient DNA. Disadvantages of these methods are high costs, long turnaround times, and need for donor DNA. Therefore, we sought to develop a rapid and cost-effective method using digital droplet PCR (ddPCR). METHODS Plasma samples were collected from stable recipients after liver (LTx, n = 10), kidney (KTx, n = 9), and heart (HTx, n = 8) transplantation as well as from 7 additional patients directly after LTx. Known single-nucleotide polymorphisms were selected for high minor allelic frequencies, of which 41 hydrolysis probe assays were established. Plasma cfDNA was preamplified, followed by conventional real-time PCR to define informative (heterologous) SNPs, which were then used for quantification (percentage) of graft-derived cfDNA (GcfDNA) using ddPCR. RESULTS Mean recovery was 94% (SD, 13%) with an imprecision of 4%–14% with the use of controls with 2% minor allele. GcfDNA in stable patients was <6.8% (LTx), <2.5% (KTx), and <3.4% (HTx). On the day of LTx, GcfDNA was approximately 90% and by day 10 it was <15% in complication-free LTx recipients. In 2 patients with biopsy-proven rejection, GcfDNA increased to >60%, whereas in 1 patient with cholestasis no increase was found. CONCLUSIONS A novel, cost-effective, rapid technique was developed to quantify GcfDNA in transplant recipients. This technique embodies a promising, potentially universal biomarker for early detection of rejection, which could enable more effective therapeutic interventions."],["dc.identifier.doi","10.1373/clinchem.2013.210328"],["dc.identifier.pmid","24061615"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/65680"],["dc.language.iso","en"],["dc.relation.eissn","1530-8561"],["dc.relation.issn","0009-9147"],["dc.title","Digital droplet PCR for rapid quantification of donor DNA in the circulation of transplant recipients as a potential universal biomarker of graft injury"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","S107"],["dc.bibliographiccitation.journal","Liver Transplantation"],["dc.bibliographiccitation.lastpage","S108"],["dc.bibliographiccitation.volume","20"],["dc.contributor.author","Slotta, Jan Erik"],["dc.contributor.author","Beck, Julia"],["dc.contributor.author","Birau, Sarah"],["dc.contributor.author","Balzer, Stefan"],["dc.contributor.author","Andag, Reiner"],["dc.contributor.author","Kanzow, Philipp"],["dc.contributor.author","Schmitz, Jessica"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Moerer, Onnen"],["dc.contributor.author","Walson, Philip D."],["dc.contributor.author","Oellerich, Michael"],["dc.contributor.author","Schuetz, Eckehardt"],["dc.contributor.author","Kollmar, Otto"],["dc.date.accessioned","2018-11-07T09:39:07Z"],["dc.date.available","2018-11-07T09:39:07Z"],["dc.date.issued","2014"],["dc.identifier.isi","000339959601015"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/33207"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.publisher.place","Hoboken"],["dc.relation.conference","Joint International Congress of ILTS, ELITA and LICAGE"],["dc.relation.eventlocation","London, ENGLAND"],["dc.relation.issn","1527-6473"],["dc.relation.issn","1527-6465"],["dc.title","Quantification of Donor DNA in the Circulation after Liver Transplantation As a Potential Universal Rejection Biomarker Using Digital Droplet PCR."],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","e43"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Transplantation Journal"],["dc.bibliographiccitation.lastpage","e45"],["dc.bibliographiccitation.volume","98"],["dc.contributor.author","Kanzow, Philipp"],["dc.contributor.author","Kollmar, Otto"],["dc.contributor.author","Schütz, Ekkehard"],["dc.contributor.author","Oellerich, Michael"],["dc.contributor.author","Schmitz, Jessica"],["dc.contributor.author","Beck, Julia"],["dc.contributor.author","Walson, Philip D."],["dc.contributor.author","Slotta, Jan Erik"],["dc.date.accessioned","2018-11-07T09:35:15Z"],["dc.date.accessioned","2020-05-22T07:54:43Z"],["dc.date.available","2018-11-07T09:35:15Z"],["dc.date.available","2020-05-22T07:54:43Z"],["dc.date.issued","2014"],["dc.identifier.isi","000341854800007"],["dc.identifier.pmid","25171533"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/65700"],["dc.language.iso","en"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation.eissn","1534-6080"],["dc.relation.issn","0041-1337"],["dc.title","Graft-Derived Cell-Free DNA as an Early Organ Integrity Biomarker After Transplantation of a Marginal HELLP Syndrome Donor Liver"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","136"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Therapeutic Drug Monitoring"],["dc.bibliographiccitation.lastpage","140"],["dc.bibliographiccitation.volume","36"],["dc.contributor.author","Oellerich, Michael"],["dc.contributor.author","Schütz, Ekkehard"],["dc.contributor.author","Kanzow, Philipp"],["dc.contributor.author","Schmitz, Jessica"],["dc.contributor.author","Beck, Julia"],["dc.contributor.author","Kollmar, Otto"],["dc.contributor.author","Streit, Frank"],["dc.contributor.author","Walson, Philip D."],["dc.date.accessioned","2018-11-07T09:41:38Z"],["dc.date.accessioned","2020-05-22T07:08:44Z"],["dc.date.available","2018-11-07T09:41:38Z"],["dc.date.available","2020-05-22T07:08:44Z"],["dc.date.issued","2014"],["dc.description.abstract","Background:Immunosuppressant therapeutic ranges for transplant patients have traditionally been established by indirect clinical means. However, liquid biopsy methods measuring graft-derived cell-free DNA (GcfDNA) in blood directly interrogate donor organ integrity. This study was performed to determine whether GcfDNA quantification could be used to reexamine minimally effective trough tacrolimus (Tacro) concentrations in liver transplantation (LTx) patients.Methods:As part of a large prospective study to demonstrate the ability of GcfDNA to identify early graft rejection, 10 adult white LTx patients [8 men, 2 women, 3 hepatitis C virus (HCV) positive; mean SD age (years) = 56 9.4] had simultaneous GcfDNA and whole-blood trough Tacro concentrations measured between days 5 and 30 after LTx. Samples were analyzed using droplet digital polymerase chain reaction for GcfDNA and liquid chromatography tandem mass spectrometry for Tacro. GcfDNA and trough Tacro concentrations were then compared to identify Tacro concentrations associated with intact graft integrity.Results:Although there were large individual differences, there was a highly significant (Fisher P = 0.00002) segregation between whole-blood Tacro concentrations of 8 g/L and normal (10%) GcfDNA percentages. The best discrimination in this population between effective and ineffective trough Tacro concentrations was estimated to be at 6.8 g/L (P < 10(-7)). Compared with HCV- patients (n = 7), the 3 HCV+ patients had more variable associations between GcfDNA percentages and Tacro concentrations.Conclusions:Direct measurement of graft integrity using GcfDNA was useful to confirm the lower limit of the therapeutic ranges for trough Tacro concentrations after LTx. It would probably be useful to do so also for other immunosuppressant drugs and after other solid organ transplants. The method might be especially useful to detect graft injury during immunosuppressant dose minimization strategies."],["dc.description.sponsorship","German Federal Ministry of Education and Research [FKZ: 01ES1102]"],["dc.identifier.doi","10.1097/FTD.0000000000000044"],["dc.identifier.isi","000333200900002"],["dc.identifier.pmid","24452066"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/65681"],["dc.language.iso","en"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation.eissn","1536-3694"],["dc.relation.issn","0163-4356"],["dc.title","Use of Graft-Derived Cell-Free DNA as an Organ Integrity Biomarker to Reexamine Effective Tacrolimus Trough Concentrations After Liver Transplantation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]