Macher Hada C, Suárez-Artacho Gonzalo, Guerrero Juan M, Gómez-Bravo Miguel A, Álvarez-Gómez Sara, Bernal-Bellido Carmen, Dominguez-Pascual Inmaculada, Rubio Amalia
Dpt. of Clinical Biochemistry, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Seville, Spain.
Hepatobiliary and Liver Transplantation Unit, Virgen del Rocío University Hospital, Seville, Spain.
PLoS One. 2014 Dec 9;9(12):e113987. doi: 10.1371/journal.pone.0113987. eCollection 2014.
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.
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.
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.
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.
由于器官移植受者的长期存活与健康器官维持之间的关系，移植器官的健康评估非常重要。如今，测量移植受者循环中来自移植物的游离DNA已被视为器官排斥或移植相关并发症的潜在生物标志物，旨在替代或减少肝活检。然而，迄今为止开发的方法昂贵且极其耗时。我们的方法是在男性供体器官的性别不匹配女性受者中，测量作为男性器官生物标志物的SRY基因。
在移植再灌注时（第0天）以及在重症监护病房停留期间，预先通过实时定量PCR对SRY基因进行游离DNA定量。还对β-珠蛋白游离DNA水平进行了定量，β-珠蛋白是一种一般细胞损伤标志物。
在术后第一周接受移植物且无任何并发症的患者，其β-珠蛋白平均值从第0天到患者病情稳定期间有所下降。在发生某种移植后并发症的患者中，这种下降并不明显。所有患者在第0天SRY水平均升高，住院期间下降。未损害捐赠器官的不同并发症显示β-珠蛋白水平升高，但SRY基因水平未升高。然而，当捐赠器官受损时，患者两种基因水平均升高。
在女性受者血清中测定SRY基因是捐赠器官的一种明确且特异的生物标志物，并且通过一种非昂贵技术可在短时间内为我们提供有关移植物健康的重要信息。这种方法可能使临床医生能够对移植患者进行密切随访。
