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...

Full description

Bibliographic Details
Main Authors: Li Li, Kiran Khush, Szu-Chuan Hsieh, Lihua Ying, Helen Luikart, Tara Sigdel, Silke Roedder, Andrew Yang, Hannah Valantine, Minnie M Sarwal
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3864873?pdf=render
_version_ 1811273647615115264
author Li Li
Kiran Khush
Szu-Chuan Hsieh
Lihua Ying
Helen Luikart
Tara Sigdel
Silke Roedder
Andrew Yang
Hannah Valantine
Minnie M Sarwal
author_facet Li Li
Kiran Khush
Szu-Chuan Hsieh
Lihua Ying
Helen Luikart
Tara Sigdel
Silke Roedder
Andrew Yang
Hannah Valantine
Minnie M Sarwal
author_sort Li Li
collection DOAJ
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.
first_indexed 2024-04-12T23:04:13Z
format Article
id doaj.art-ff5aee69dbda4bc6beb30743c0f7243e
institution Directory Open Access Journal
issn 1932-6203
language English
last_indexed 2024-04-12T23:04:13Z
publishDate 2013-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj.art-ff5aee69dbda4bc6beb30743c0f7243e2022-12-22T03:12:59ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01812e8215310.1371/journal.pone.0082153Identification of common blood gene signatures for the diagnosis of renal and cardiac acute allograft rejection.Li LiKiran KhushSzu-Chuan HsiehLihua YingHelen LuikartTara SigdelSilke RoedderAndrew YangHannah ValantineMinnie M SarwalTo 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.http://europepmc.org/articles/PMC3864873?pdf=render
spellingShingle Li Li
Kiran Khush
Szu-Chuan Hsieh
Lihua Ying
Helen Luikart
Tara Sigdel
Silke Roedder
Andrew Yang
Hannah Valantine
Minnie M Sarwal
Identification of common blood gene signatures for the diagnosis of renal and cardiac acute allograft rejection.
PLoS ONE
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
url http://europepmc.org/articles/PMC3864873?pdf=render
work_keys_str_mv AT lili identificationofcommonbloodgenesignaturesforthediagnosisofrenalandcardiacacuteallograftrejection
AT kirankhush identificationofcommonbloodgenesignaturesforthediagnosisofrenalandcardiacacuteallograftrejection
AT szuchuanhsieh identificationofcommonbloodgenesignaturesforthediagnosisofrenalandcardiacacuteallograftrejection
AT lihuaying identificationofcommonbloodgenesignaturesforthediagnosisofrenalandcardiacacuteallograftrejection
AT helenluikart identificationofcommonbloodgenesignaturesforthediagnosisofrenalandcardiacacuteallograftrejection
AT tarasigdel identificationofcommonbloodgenesignaturesforthediagnosisofrenalandcardiacacuteallograftrejection
AT silkeroedder identificationofcommonbloodgenesignaturesforthediagnosisofrenalandcardiacacuteallograftrejection
AT andrewyang identificationofcommonbloodgenesignaturesforthediagnosisofrenalandcardiacacuteallograftrejection
AT hannahvalantine identificationofcommonbloodgenesignaturesforthediagnosisofrenalandcardiacacuteallograftrejection
AT minniemsarwal identificationofcommonbloodgenesignaturesforthediagnosisofrenalandcardiacacuteallograftrejection