Session Time: 4:00pm-5:30pm
Presentation Time: 5:12pm-5:24pm
Location: Terrace IV
Background: Previous studies with cross-organ transcriptional analysis of 794 allograft biopsies from kidney, liver, heart and lung transplant patients identified a common rejection module (CRM) of 11 genes by microarray analysis. It has been previously demonstrated that the expression of these 11 genes is a highly sensitive marker for acute rejection (AR) in kidney transplant. Here we apply the CRM score to renal transplant biopsies with and without rejection to validate these findings.
Methods: An independent validation study was conducted to set the CRM diagnostic threshold for alloimmune inflammation and rejection by QPCR of the 11 CRM genes in 61 renal allograft biopsies with and without acute rejection; 18S was used as the housekeeping control. All patients had 6 and 24 month protocol biopsies, in addition to the indicated AR biopsy, and follow-up for clinical graft function. Using gene expression results by QPCR, a composite CRM score was calculated for each sample across all 11 genes. Significant differences between stable (no-AR) and AR were determined by unpaired 2-tailed t tests or Mann-U Whitney, while sensitivity and specificity were determined by area under the curve calculated in SPSS.
Results: A threshold of a CRM score of 1.89 differentiated acute rejection samples with 87.5% sensitivity and 86.2% specificity (AUC= .918, 95% CI=0.839-0.998). In addition, among the no-AR cohort, 8 of the patients showed accelerated chronic changes on 24 month biopsies with significantly greater CRM scores than those without progressive chronicity (mean = 5.11± 4.07 and 1.27± 1.6, respectively, p-value = 0.034).
Conclusions: A biopsy rapid QPCR assay for 11 genes accurately detects kidney transplants with acute rejection from those with stable renal function and no rejection. More importantly, the score identifies early subclinical molecular inflammation in protocol biopsies that are otherwise histologically normal, but are at high risk for accelerated chronicity due to persistent subclinical inflammation. The inclusion of the CRM score as a molecular monitoring tool with protocol biopsies may provide prognostic information for histologically undetected, sub-clinical graft inflammation that drives subsequent allograft injury.
To cite this abstract in AMA style:Ng Y, Roedder S, Bestard O, Sigdel T, Hsieh S-C, Sarwal M. Intra-Allograft Common Rejection Module (CRM) Expression in Kidney Transplants Diagnoses Acute Rejection and Predicts Long Term Graft Prognosis [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/intra-allograft-common-rejection-module-crm-expression-in-kidney-transplants-diagnoses-acute-rejection-and-predicts-long-term-graft-prognosis/. Accessed February 23, 2019.
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