Monitoring of transplanted liver health by quantification of organ-specific genomic marker in circulating DNA from receptor

PLoS One. 2014 Dec 9;9(12):e113987. doi: 10.1371/journal.pone.0113987. eCollection 2014.

Abstract

Background: Health assessment of the transplanted organ is very important due to the relationship of long-term survival of organ transplant recipients and health organ maintenance. Nowadays, the measurement of cell-free DNA from grafts in the circulation of transplant recipients has been considered a potential biomarker of organ rejection or transplant associated complications in an attempt to replace or reduce liver biopsy. However, methods developed to date are expensive and extremely time-consuming. Our approach was to measure the SRY gene, as a male organ biomarker, in a setting of sex-mismatched female recipients of male donor organs.

Methods: Cell-free DNA quantization of the SRY gene was performed by real-time quantitative PCR beforehand, at the moment of transplantation during reperfusion (day 0) and during the stay at the intensive care unit. Beta-globin cell-free DNA levels, a general cellular damage marker, were also quantified.

Results: Beta-globin mean values of patients, who accepted the graft without any complications during the first week after surgery, diminished from day 0 until patient stabilization. This decrease was not so evident in patients who suffered some kind of post-transplantation complications. All patients showed an increase in SRY levels at day 0, which decreased during hospitalization. Different complications that did not compromise donated organs showed increased beta-globin levels but no SRY gene levels. However, when a donated organ was damaged the patients exhibited high levels of both genes.

Conclusion: Determination of a SRY gene in a female recipient's serum is a clear and specific biomarker of donated organs and may give us important information about graft health in a short period of time by a non-expensive technique. This approach may permit clinicians to maintain a close follow up of the transplanted patient.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Chromosomes, Human, Y / genetics
  • DNA / blood*
  • DNA / isolation & purification
  • Female
  • Genetic Markers*
  • Genomics*
  • Humans
  • Liver Transplantation*
  • Male
  • Middle Aged
  • Organ Specificity
  • Sex-Determining Region Y Protein / blood
  • Transplant Recipients*
  • beta-Globins / metabolism

Substances

  • Genetic Markers
  • SRY protein, human
  • Sex-Determining Region Y Protein
  • beta-Globins
  • DNA

Grants and funding

The work was supported by “Red temática de investigación cooperativa en envejecimiento y fragilidad” (RETICEF RD06/00130001), and by “Ayuda para la Consolidación de Grupos de Investigación y Desarrollo Tecnológico de la Comunidad Autónoma Andaluza” (P06-CTS-0160). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.