A peripheral blood diagnostic test for acute rejection in renal transplantation

L. Li, P. Khatri, T. K. Sigdel, T. Tran, L. Ying, M. J. Vitalone, A. Chen, S. Hsieh, H. Dai, M. Zhang, M. Naesens, V. Zarkhin, P. Sansanwal, R. Chen, M. Mindrinos, W. Xiao, M. Benfield, R. B. Ettenger, V. Dharnidharka, R. MathiasA. Portale, R. McDonald, W. Harmon, D. Kershaw, V. M. Vehaskari, E. Kamil, H. J. Baluarte, B. Warady, R. Davis, A. J. Butte, O. Salvatierra, M. M. Sarwal

Research output: Contribution to journalArticlepeer-review

91 Scopus citations

Abstract

Monitoring of renal graft status through peripheral blood (PB) rather than invasive biopsy is important as it will lessen the risk of infection and other stresses, while reducing the costs of rejection diagnosis. Blood gene biomarker panels were discovered by microarrays at a single center and subsequently validated and cross-validated by QPCR in the NIH SNSO1 randomized study from 12 US pediatric transplant programs. A total of 367 unique human PB samples, each paired with a graft biopsy for centralized, blinded phenotype classification, were analyzed (115 acute rejection (AR), 180 stable and 72 other causes of graft injury). Of the differentially expressed genes by microarray, Q-PCR analysis of a five gene-set (DUSP1, PBEF1, PSEN1, MAPK9 and NKTR) classified AR with high accuracy. A logistic regression model was built on independent training-set (n = 47) and validated on independent test-set (n = 198)samples, discriminating AR from STA with 91% sensitivity and 94% specificity and AR from all other non-AR phenotypes with 91% sensitivity and 90% specificity. The 5-gene set can diagnose AR potentially avoiding the need for invasive renal biopsy. These data support the conduct of a prospective study to validate the clinical predictive utility of this diagnostic tool. This study documents the development of a blood-based gene panel for the noninvasive diagnosis of biopsy-proven acute kidney allograft rejection, and in doing so provides the basis for a blood test for acute rejection. See editorial by Bromberg and Iklé on page 2573.

Original languageEnglish
Pages (from-to)2710-2718
Number of pages9
JournalAmerican Journal of Transplantation
Volume12
Issue number10
DOIs
StatePublished - Oct 2012

Keywords

  • Acute allograft rejection
  • bioinformatics
  • biomarker
  • renal allograft rejection
  • renal transplantation
  • translational research
  • transplant rejection
  • transplantation
  • transplantation genomics

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