Proteoforms in Peripheral Blood Mononuclear Cells as Novel Rejection Biomarkers in Liver Transplant Recipients.

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Proteoforms in Peripheral Blood Mononuclear Cells as Novel Rejection Biomarkers in Liver Transplant Recipients.

http://www.dekart.com/?holdredge-master-thesis-limestone Holdredge Master Thesis Limestone Am J Transplant. 2017 May 16;:

Research Paper Hospitality And Customer Relationship Management Authors: Toby TK, Abecassis M, Kim K, Thomas PM, Fellers RT, LeDuc RD, Kelleher NL, Demetris J, Levitsky J

Abstract Biomarker profiles of acute rejection in liver transplant recipients could enhance the diagnosis and management of recipients. Our aim was to identify diagnostic proteoform signatures of acute rejection in circulating immune cells, using an emergent "top down" proteomics methodology. We prepared differentially processed and cryopreserved cell lysates from 26 non-viral liver transplant recipients by molecular weight-based fractionation and analyzed them by mass spectrometry of whole proteins in three steps: 1) Nanocapillary liquid chromatography coupled with high-resolution tandem mass spectrometry; 2) database searching to identify and characterize intact proteoforms; 3) data processing through a hierarchical linear model matching the study design to quantify proteoform fold changes in patients with rejection vs. normal liver function vs. acute dysfunction without rejection. Differentially expressed proteoforms were seen in patients with rejection vs. normal and non-specific controls, most evidently in the cell preparations stored in traditional serum-rich media. Mapping analysis of these proteins back to genes through gene ontology and pathway analysis tools revealed multiple signaling pathways, including inflammation mediated by cytokines and chemokines. Larger studies are needed to validate these novel rejection signatures and test their predictive value for use in clinical management. This article is protected by copyright. All rights reserved.

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PMID: 28510335 [PubMed - as supplied by publisher]

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