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Am J Transplant. 2013 Apr;13(4):971-983. doi: 10.1111/ajt.12150. Epub 2013 Feb 15.

Molecular diagnosis of antibody-mediated rejection in human kidney transplants.

Author information

1
Alberta Transplant Applied Genomics Centre, Edmonton, Alberta.
2
Servei de Nefrologia, Hospital de la Vall d'Hebron, Barcelona, Spain.
3
Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada.
4
Kidney Transplant Department, Necker Hospital, Paris, France.
5
Department of Anatomical Pathology, Austin Hospital, Heidelberg, Victoria, Australia.
6
Department of Renal Medicine, Manchester Royal Infirmary, Manchester, UK.
7
Department of Medicine, Division of Nephrology and Transplant Immunology, University of Alberta, Edmonton, AB, Canada.

Abstract

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.

PMID:
23414212
DOI:
10.1111/ajt.12150
[Indexed for MEDLINE]
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