title: Identification of common blood gene signatures for the diagnosis of renal and cardiac acute allograft rejection.
abstract: 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.
authors.affiliation: Department of Pediatrics, Stanford University, Palo Alto, California, United States of America.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Palo Alto, California, United States of America.
authors.forename: Kiran
authors.initials: K
authors.lastname: Khush
authors.affiliation: Department of Pediatrics, Stanford University, Palo Alto, California, United States of America ; California Pacific Medical Center Research Institute, San Francisco, California, United States of America.
authors.forename: Szu-Chuan
authors.initials: SC
authors.lastname: Hsieh
authors.affiliation: Department of Pediatrics, Stanford University, Palo Alto, California, United States of America.
authors.forename: Lihua
authors.initials: L
authors.lastname: Ying
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Palo Alto, California, United States of America.
authors.forename: Helen
authors.initials: H
authors.lastname: Luikart
authors.affiliation: Department of Pediatrics, Stanford University, Palo Alto, California, United States of America ; California Pacific Medical Center Research Institute, San Francisco, California, United States of America.
authors.forename: Tara
authors.initials: T
authors.lastname: Sigdel
authors.affiliation: Department of Pediatrics, Stanford University, Palo Alto, California, United States of America ; California Pacific Medical Center Research Institute, San Francisco, California, United States of America.
authors.forename: Silke
authors.initials: S
authors.lastname: Roedder
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Palo Alto, California, United States of America.
authors.forename: Andrew
authors.initials: A
authors.lastname: Yang
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Palo Alto, California, United States of America.
authors.forename: Hannah
authors.initials: H
authors.lastname: Valantine
authors.affiliation: Department of Pediatrics, Stanford University, Palo Alto, California, United States of America ; California Pacific Medical Center Research Institute, San Francisco, California, United States of America.
authors.forename: Minnie M
authors.initials: MM
authors.lastname: Sarwal
mesh_terms: D000328:Adult; D000368:Aged; D064591:Allografts; D015415:Biomarkers / Q000097:blood; D003586:Cytomegalovirus Infections / Q000097:blood / Q000150:complications*; D005260:Female; D015870:Gene Expression; D006084:Graft Rejection / Q000097:blood / Q000150:complications / Q000175:diagnosis*; D016027:Heart Transplantation; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged
chemical_list: D015415:Biomarkers