To validate a peripheral blood transcriptional biomarker panel diagnostic for acute renal allograft rejection for the diagnosis and prediction of acute cardiac allograft rejection we analyzed ten biomarkers of renal allograft rejection that were previously identified via high-throughput microarray and Q-PCR studies by Q-PCR in 141 peripheral blood samples from 45 consecutive heart transplant recipients at Stanford University from 2002-2005. Following sample groups were investigated: stable graft function with no evidence of cellular rejection (STA, n=41), biopsy proven acute allograft rejection (AR=66), CMV infection without AR (CMV, n=12), and post/pre-AR for samples drawn within 6 months before or after an episode of AR (n=23). AR was diagnosed by endomyocardial biopsy using the 1990 ISHLT classification system. Blood samples drawn during clinically-significant AR (ISHLT Grade ≥3, n=11) and 21 randomly selected STA samples were used in the training-set to develop a predictive logistic regression model. This model was tested for AR classification in independent prediction set-1, comprised of 55 AR samples (ISHLT Grade ≤2), 19 STA samples, and 12 CMV samples, and for AR prediction in independent prediction set-2, composed of 23 pre-post/AR samples.
The multinomial logistic regression model with the best classification performance for AR prediction was a 5-gene model with an ROC score of 89%. When applied to prediction set-1, the model predicted AR with 89% sensitivity, 90% specificity, and 89% accuracy. CMV was ruled out as a confounder of AR. When applied to prediction set-2, and blood samples drawn six months prior to biopsy proven-rejection the model performed with 80% sensitivity for AR prediction; predicted AR probabilities remained consistently high (mean 87%) in the samples drawn within 6 months after episodes of untreated AR (ISHLT Grade ≤2).
A 5 peripheral blood biomarker panel initially identified in the setting of renal transplant rejection may be used to predict AR in heart transplant recipients. Serial utilization of this 5-gene profile after transplantation may be a valuable non-invasive method for prediction and diagnosis of AR after heart transplantation.
To cite this abstract in AMA style:Roedder S, Li L, Kush K, Hsieh S, Luikart H, Yang A, Valentine H, Sarwal M. Identification of Common Blood-Based Biomarker Gene Panels for the Diagnosis of Renal and Cardiac Acute Allograft Rejection [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/identification-of-common-blood-based-biomarker-gene-panels-for-the-diagnosis-of-renal-and-cardiac-acute-allograft-rejection/. Accessed August 10, 2020.
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