Journal
AMERICAN JOURNAL OF TRANSPLANTATION
Volume 13, Issue 4, Pages 971-983Publisher
WILEY
DOI: 10.1111/ajt.12150
Keywords
Antibody-mediated rejection; classifier; kidney transplant; microarrays; molecular diagnostics
Categories
Funding
- Novartis Pharma AG
- Genome Canada
- University Of Alberta Hospital Foundation
- Roche Molecular Systems
- Hoffmann-La Roche Canada Ltd.
- Alberta Ministry of Advanced Education and Technology
- Roche Organ Transplant Research Foundation
- Astellas
Ask authors/readers for more resources
Antibody-mediated rejection is the major cause of kidney transplant failure, but the histology-based diagnostic system misses most cases due to its requirement for C4d positivity. We hypothesized that gene expression data could be used to test biopsies for the presence of antibody-mediated rejection. To develop a molecular test, we prospectively assigned diagnoses, including C4d-negative antibody-mediated rejection, to 403 indication biopsies from 315 patients, based on histology (microcirculation lesions) and donor-specific HLA antibody. We then used microarray data to develop classifiers that assigned antibody-mediated rejection scores to each biopsy. The transcripts distinguishing antibody-mediated rejection from other conditions were mostly expressed in endothelial cells or NK cells, or were IFNG-inducible. The scores correlated with the presence of microcirculation lesions and donor-specific antibody. Of 45 biopsies with scores >0.5, 39 had been diagnosed as antibody-mediated rejection on the basis of histology and donor-specific antibody. High scores were also associated with unanimity among pathologists that antibody-mediated rejection was present. The molecular score also strongly predicted future graft loss in Cox regression analysis. We conclude that microarray assessment of gene expression can assign a probability of ABMR to transplant biopsies without knowledge of HLA antibody status, histology, or C4d staining, and predicts future failure.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available