Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8737630 | Human Immunology | 2018 | 30 Pages |
Abstract
We developed urinary cell messenger RNA (mRNA) profiling to monitor in vivo status of human kidney allografts based on our conceptualization that the kidney allograft may function as an in vivo flow cell sorter allowing access of graft infiltrating cells to the glomerular ultrafiltrate and that interrogation of urinary cells is informative of allograft status. For the profiling urinary cells, we developed a two-step preamplification enhanced real-time quantitative PCR (RT-QPCR) assays with a customized amplicon; preamplification compensating for the low RNA yield from urine and the customized amplicon facilitating absolute quantification of mRNA and overcoming the inherent limitations of relative quantification widely used in RT-QPCR assays. Herein, we review our discovery and validation of urinary cell mRNAs as noninvasive biomarkers prognostic and diagnostic of acute cellular rejection (ACR) in kidney allografts. We summarize our results reflecting the utility of urinary cell mRNA profiling for predicting reversal of ACR with anti-rejection therapy; differential diagnosis of kidney allograft dysfunction; and noninvasive diagnosis and prognosis of BK virus nephropathy. Messenger RNA profiles associated with human kidney allograft tolerance are also summarized in this review. Altogether, data supporting the idea that urinary cell mRNA profiles are informative of kidney allograft status and tolerance are reviewed in this report.
Keywords
UTIrRNAPI-9BK virus nephropathyCD3εPD-L2OX40LIP-10ACRAMRRT-qPCRmRNATGF-β1FOXP3PD-1PD-L1ROCnatural killercDNAComplementary DNAmessenger RNARibosomal RNAantibody mediated rejectionPAIplasminogen activator inhibitorTransforming growth factor-β1Toleranceforkhead box P3Acute cellular rejectionreal-time quantitative PCRRejectionurinary tract infectionconfidence intervalOX40 ligandprogrammed cell death ligand-1polymerase chain reactionprogrammed cell death protein-1Kidney transplantationreceiver-operating-characteristic
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Authors
Voravech Nissaisorakarn, John Richard Lee, Michelle Lubetzky, Manikkam Suthanthiran,