Monitoring of Transplanted Liver Health by Quantification of Organ-Specific Genomic Marker in Circulating DNA from Receptor

被引:41
作者
Macher, Hada C. [1 ]
Suarez-Artacho, Gonzalo [2 ]
Guerrero, Juan M. [1 ]
Gomez-Bravo, Miguel A. [2 ]
Alvarez-Gomez, Sara [1 ]
Bernal-Bellido, Carmen [2 ]
Dominguez-Pascual, Inmaculada [1 ]
Rubio, Amalia [1 ]
机构
[1] Univ Seville, CSIC, Hosp Univ Virgen Rocio, Inst Biomed Sevilla IBiS,Dept Clin Biochem, Seville, Spain
[2] Virgen Rocio Univ Hosp, Hepatobiliary & Liver Transplantat Unit, Seville, Spain
关键词
CELL-FREE DNA; ACUTE REJECTION; RENAL-TRANSPLANTATION; GRAFT-REJECTION; DONOR DNA; RECIPIENTS; PLASMA; KIDNEY; PCR; ORIGIN;
D O I
10.1371/journal.pone.0113987
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:18
相关论文
共 22 条
[1]   The Evolution of Liver Transplantation During 3 Decades Analysis of 5347 Consecutive Liver Transplants at a Single Center [J].
Agopian, Vatche G. ;
Petrowsky, Henrik ;
Kaldas, Fady M. ;
Zarrinpar, Ali ;
Farmer, Douglas G. ;
Yersiz, Hasan ;
Holt, Curtis ;
Harlander-Locke, Michael ;
Hong, Johnny C. ;
Rana, Abbas R. ;
Venick, Robert ;
McDiarmid, Sue V. ;
Goldstein, Leonard I. ;
Durazo, Francisco ;
Saab, Sammy ;
Han, Steven ;
Xia, Victor ;
Hiatt, Jonathan R. ;
Busuttil, Ronald W. .
ANNALS OF SURGERY, 2013, 258 (03) :409-421
[2]   Digital Droplet PCR for Rapid Quantification of Donor DNA in the Circulation of Transplant Recipients as a Potential Universal Biomarker of Graft Injury [J].
Beck, Julia ;
Bierau, Sarah ;
Balzer, Stefan ;
Andag, Reiner ;
Kanzow, Philipp ;
Schmitz, Jessica ;
Gaedcke, Jochen ;
Moerer, Onnen ;
Slotta, Jan E. ;
Walson, Philip ;
Kollmar, Otto ;
Oellerich, Michael ;
Schuetz, Ekkehard .
CLINICAL CHEMISTRY, 2013, 59 (12) :1732-1741
[3]   Noninvasive Identification and Monitoring of Cancer Mutations by Targeted Deep Sequencing of Plasma DNA [J].
Forshew, Tim ;
Murtaza, Muhammed ;
Parkinson, Christine ;
Gale, Davina ;
Tsui, Dana W. Y. ;
Kaper, Fiona ;
Dawson, Sarah-Jane ;
Piskorz, Anna M. ;
Jimenez-Linan, Mercedes ;
Bentley, David ;
Hadfield, James ;
May, Andrew P. ;
Caldas, Carlos ;
Brenton, James D. ;
Rosenfeld, Nitzan .
SCIENCE TRANSLATIONAL MEDICINE, 2012, 4 (136)
[4]   Soluble donor DNA concentrations in recipient serum correlate with pancreas-kidney rejection [J].
Gadi, VK ;
Nelson, JL ;
Boespflug, ND ;
Guthrie, KA ;
Kuhr, CS .
CLINICAL CHEMISTRY, 2006, 52 (03) :379-382
[5]   Cell-Free DNA as a Noninvasive Acute Rejection Marker in Renal Transplantation [J].
Garcia Moreira, Vanessa ;
Prieto Garcia, Belen ;
Baltar Martin, Jose M. ;
Ortega Suarez, Francisco ;
Alvarez, Francisco V. .
CLINICAL CHEMISTRY, 2009, 55 (11) :1958-1966
[6]  
Grant A., 1999, Gut, V45, pIV1
[7]   Transplantation Monitoring by Plasma DNA Sequencing [J].
Lo, Y. M. Dennis .
CLINICAL CHEMISTRY, 2011, 57 (07) :941-942
[8]   Presence of donor-specific DNA in plasma of kidney and liver-transplant recipients [J].
Lo, YMD ;
Tein, MSC ;
Pang, CCP ;
Yeung, CK ;
Tong, KL ;
Hjelm, NM .
LANCET, 1998, 351 (9112) :1329-1330
[9]   Origin of plasma cell-free DNA after solid organ transplantation [J].
Lui, YYN ;
Woo, KS ;
Wang, AYM ;
Yeung, CK ;
Li, PKT ;
Chau, E ;
Ruygrok, P ;
Lo, YMD .
CLINICAL CHEMISTRY, 2003, 49 (03) :495-496
[10]   Role of early cell-free DNA levels decrease as a predictive marker of fatal outcome after severe traumatic brain injury [J].
Macher, Hada ;
Egea-Guerrero, Juan J. ;
Revuelto-Rey, Jaume ;
Gordillo-Escobar, Elena ;
Enamorado-Enamorado, Judy ;
Boza, Antonio ;
Rodriguez, Ana ;
Molinero, Patrocinio ;
Guerrero, Juan M. ;
Dominguez-Roldan, Jose M. ;
Murillo-Cabezas, Francisco ;
Rubio, Amalia .
CLINICA CHIMICA ACTA, 2012, 414 :12-17