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Identification of Common Blood Gene Signatures for the Diagnosis of Renal and Cardiac Acute Allograft Rejection

To test, whether 10 genes, diagnostic of renal allograft rejection in blood, are able to diagnose and predict cardiac allograft rejection, we analyzed 250 blood samples from heart transplant recipients with and without acute rejection (AR) and with cytomegalovirus (CMV) infection by QPCR. A QPCR-bas...

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Autores principales: Li, Li, Khush, Kiran, Hsieh, Szu-Chuan, Ying, Lihua, Luikart, Helen, Sigdel, Tara, Roedder, Silke, Yang, Andrew, Valantine, Hannah, Sarwal, Minnie M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3864873/
https://www.ncbi.nlm.nih.gov/pubmed/24358149
http://dx.doi.org/10.1371/journal.pone.0082153
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author Li, Li
Khush, Kiran
Hsieh, Szu-Chuan
Ying, Lihua
Luikart, Helen
Sigdel, Tara
Roedder, Silke
Yang, Andrew
Valantine, Hannah
Sarwal, Minnie M.
author_facet Li, Li
Khush, Kiran
Hsieh, Szu-Chuan
Ying, Lihua
Luikart, Helen
Sigdel, Tara
Roedder, Silke
Yang, Andrew
Valantine, Hannah
Sarwal, Minnie M.
author_sort Li, Li
collection PubMed
description To test, whether 10 genes, diagnostic of renal allograft rejection in blood, are able to diagnose and predict cardiac allograft rejection, we analyzed 250 blood samples from heart transplant recipients with and without acute rejection (AR) and with cytomegalovirus (CMV) infection by QPCR. A QPCR-based logistic regression model was built on 5 of these 10 genes (AR threshold composite score>37% = AR) and tested for AR prediction in an independent set of 109 samples, where it correctly diagnosed AR with 89% accuracy, with no misclassifications for AR ISHLT grade 1b. CMV infection did not confound the AR score. The genes correctly diagnosed AR in a blood sample within 6 months prior to biopsy diagnosis with 80% sensitivity and untreated grade 1b AR episodes had persistently elevated scores until 6 months after biopsy diagnosis. The gene score was also correlated with presence or absence of cardiac allograft vasculopathy (CAV) irrespective of rejection grade. In conclusion, there is a common transcriptional axis of immunological trafficking in peripheral blood in both renal and cardiac organ transplant rejection, across a diverse recipient age range. A common gene signature, initially identified in the setting of renal transplant rejection, can be utilized serially after cardiac transplantation, to diagnose and predict biopsy confirmed acute heart transplant rejection.
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spelling pubmed-38648732013-12-19 Identification of Common Blood Gene Signatures for the Diagnosis of Renal and Cardiac Acute Allograft Rejection Li, Li Khush, Kiran Hsieh, Szu-Chuan Ying, Lihua Luikart, Helen Sigdel, Tara Roedder, Silke Yang, Andrew Valantine, Hannah Sarwal, Minnie M. PLoS One Research Article To test, whether 10 genes, diagnostic of renal allograft rejection in blood, are able to diagnose and predict cardiac allograft rejection, we analyzed 250 blood samples from heart transplant recipients with and without acute rejection (AR) and with cytomegalovirus (CMV) infection by QPCR. A QPCR-based logistic regression model was built on 5 of these 10 genes (AR threshold composite score>37% = AR) and tested for AR prediction in an independent set of 109 samples, where it correctly diagnosed AR with 89% accuracy, with no misclassifications for AR ISHLT grade 1b. CMV infection did not confound the AR score. The genes correctly diagnosed AR in a blood sample within 6 months prior to biopsy diagnosis with 80% sensitivity and untreated grade 1b AR episodes had persistently elevated scores until 6 months after biopsy diagnosis. The gene score was also correlated with presence or absence of cardiac allograft vasculopathy (CAV) irrespective of rejection grade. In conclusion, there is a common transcriptional axis of immunological trafficking in peripheral blood in both renal and cardiac organ transplant rejection, across a diverse recipient age range. A common gene signature, initially identified in the setting of renal transplant rejection, can be utilized serially after cardiac transplantation, to diagnose and predict biopsy confirmed acute heart transplant rejection. Public Library of Science 2013-12-16 /pmc/articles/PMC3864873/ /pubmed/24358149 http://dx.doi.org/10.1371/journal.pone.0082153 Text en © 2013 Li et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Li, Li
Khush, Kiran
Hsieh, Szu-Chuan
Ying, Lihua
Luikart, Helen
Sigdel, Tara
Roedder, Silke
Yang, Andrew
Valantine, Hannah
Sarwal, Minnie M.
Identification of Common Blood Gene Signatures for the Diagnosis of Renal and Cardiac Acute Allograft Rejection
title Identification of Common Blood Gene Signatures for the Diagnosis of Renal and Cardiac Acute Allograft Rejection
title_full Identification of Common Blood Gene Signatures for the Diagnosis of Renal and Cardiac Acute Allograft Rejection
title_fullStr Identification of Common Blood Gene Signatures for the Diagnosis of Renal and Cardiac Acute Allograft Rejection
title_full_unstemmed Identification of Common Blood Gene Signatures for the Diagnosis of Renal and Cardiac Acute Allograft Rejection
title_short Identification of Common Blood Gene Signatures for the Diagnosis of Renal and Cardiac Acute Allograft Rejection
title_sort identification of common blood gene signatures for the diagnosis of renal and cardiac acute allograft rejection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3864873/
https://www.ncbi.nlm.nih.gov/pubmed/24358149
http://dx.doi.org/10.1371/journal.pone.0082153
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