Circulating miRNA or circulating DNA—Potential biomarkers for organ transplant rejection

Abstract

Accurate and timely diagnosis of transplant rejection is essential for the long‐term survival of solid‐organ transplant recipients. Biopsy is the “gold standard” for the diagnosis of rejection, but this approach is a time‐consuming, expensive, and invasive process. An efficient, cheap, and noninvasive tool for monitoring of immune rejection is urgently needed. Circulating miRNA and circulating DNA can be easily amplified and quantified by PCR which could be potential biomarkers for monitoring organ survival and/or immune rejection. In this review, we briefly introduce the origins and characteristics of circulating miRNA and circulating DNA. Furthermore, we review their clinical application and potential as noninvasive biomarkers for rejection in organ transplantation. Finally, we sum up their potential as biomarkers, which may help scientists and surgeons choose the proper biomarker for routine assays.

MRI monitoring of transplanted neonatal porcine islets labeled with polyvinylpyrrolidone‐coated superparamagnetic iron oxide nanoparticles in a mouse model

“…Success with islet graft salvage following findings on MRI has been recently documented with other SPIO agents in rat models 9 . These MRI findings could complement many technologies currently being explored for monitoring of immune rejection in islet grafts, including utilizing reporter genes with fluorescent proteins to label islets, and utilizing cDNA and miRNA levels for a biochemical complement to imaging findings 46–48 …”

“…9 These MRI findings could complement many technologies currently being explored for monitoring of immune rejection in islet grafts, including utilizing reporter genes with fluorescent proteins to label islets, and utilizing cDNA and miRNA levels for a biochemical complement to imaging findings. [46][47][48] Concerning the limitations of our study, we do not have current evidence on the safety of PVP-SPIO, and the death of five of seven B6 rag -/-mice is enough to cause concern; however, this appeared to be due to early diabetic complications post-streptozotocin injection.…”

<p>Circulating nucleic acids as biomarkers for allograft injury after solid organ transplantation: current state-of-the-art</p>

“…33 Furthermore, miRNAs may be passively released from dying cells encapsulated in apoptotic bodies that effectively protect the miRNA from immediate degradation in the circulation. 19,34 Therefore, the potential use of these endogenous circulating miRNAs, which are highly stable in blood and resistant to temperature changes, as diagnostic markers for the detection of rejection following transplantation has gained a great deal of attention. 19,34 Circulating miRNAs as a non-invasive biomarker for the detection of immune-mediated rejection following transplantation were first evaluated using animal models, [35][36][37][38][39] but more recent testing using human samples has helped further our understanding of the kinetics and role of circulating human organ-specific miRNAs during acute rejection events.…”

“…[14][15][16][17] Blood-based biomarkers currently represent the "holy grail" for a minimally-invasive approach for the detection of rejection and, recently, circulating nucleic acids isolated from the plasma or urine have shown promise and have even been implemented into clinical practice (Figure 1). [18][19][20][21] Transcriptomics-based molecular diagnostics AlloMap Substantial effort has been made to develop non-invasive assays that could replace or reduce the use of EMB, especially for patients who are asymptomatic or who are >1 year post-transplant and in whom the likelihood of finding significant rejection is very low. In these patients, the probability of biopsy-related complications, although low, is more likely than the detection of subclinical allograft rejection requiring treatment.…”