title: Donor-Derived Cell-Free DNA Is a Novel Universal Biomarker for Allograft Rejection in Solid Organ Transplantation.
abstract: 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.
  
  
  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.
  
  
  RESULTS
  Immediately after engraftment, GcfDNA reaches high values (>5% of total cfDNA), with a rapid decrease to values of <0.5% within 1 week. Living-related KTx recipients show lower initial values, reflecting the absence of preservation injury. Episodes of rejection in KTx and HTx are accompanied by a significant increase of GcfDNA (>5-fold) above values in patients without complications, occurring earlier than clinical or biochemical hints to rejection. One case of rejection, which became clinically suspect after 1 year and was proven with biopsy, showed a significant 10-fold increase 3 months earlier.
  
  
  CONCLUSIONS
  The quantification of GcfDNA has the potential to detect rejection episodes at early stages, when other means of diagnosis are not effective. The method's noninvasiveness enables the monitoring recipients at intervals that are desired to catch rejections at early actionable stages to prevent full-blown rejection. This biomarker will be particularly valuable in regimens to minimize immunosuppression.
authors.affiliation: Chronix Biomedical, University Medical Center, Göttingen, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Beck
authors.affiliation: Department of Clinical Pharmacology, University Medical Center, Göttingen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Oellerich
authors.affiliation: Clinic for Thoracic and Cardiovascular Surgery, Heart and Diabetes Center NRW, Bad Oeynhausen, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Schulz
authors.affiliation: Clinic for Nephrology and Transplantation Centre, Klinikum Stuttgart, Stuttgart, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Schauerte
authors.affiliation: Department of Clinical Pharmacology, University Medical Center, Göttingen, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Reinhard
authors.affiliation: Clinic for Thoracic and Cardiovascular Surgery, Heart and Diabetes Center NRW, Bad Oeynhausen, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Fuchs
authors.affiliation: Institute for Laboratory and Transfusion Medicine, Heart and Diabetes Center NRW, Bad Oeynhausen, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Knabbe
authors.affiliation: Clinic for Thoracic and Cardiovascular Surgery, Heart and Diabetes Center NRW, Bad Oeynhausen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Zittermann
authors.affiliation: Clinic for Nephrology and Transplantation Centre, Klinikum Stuttgart, Stuttgart, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Olbricht
authors.affiliation: Clinic for Thoracic and Cardiovascular Surgery, Heart and Diabetes Center NRW, Bad Oeynhausen, Germany.
authors.forename: J F
authors.initials: JF
authors.lastname: Gummert
authors.affiliation: Central Institute for Clinical Chemistry and Laboratory Medicine, Klinikum Stuttgart, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Shipkova
authors.affiliation: Institute for Laboratory and Transfusion Medicine, Heart and Diabetes Center NRW, Bad Oeynhausen, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Birschmann
authors.affiliation: Central Institute for Clinical Chemistry and Laboratory Medicine, Klinikum Stuttgart, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Wieland
authors.affiliation: Chronix Biomedical, University Medical Center, Göttingen, Germany. Electronic address: esc@chronixbiomedical.de.
authors.forename: E
authors.initials: E
authors.lastname: Schütz
mesh_terms: D064591:Allografts; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D004247:DNA / Q000097:blood*; D006084:Graft Rejection / Q000097:blood* / Q000175:diagnosis; D016027:Heart Transplantation; D006801:Humans; D007668:Kidney; D016030:Kidney Transplantation; D016133:Polymerase Chain Reaction; D014019:Tissue Donors
chemical_list: D015415:Biomarkers; D004247:DNA