Molecular assessment of antibody-mediated rejection in human pancreas allograft biopsies
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Pancreas transplant longevity is limited by immune rejection, which is diagnosed by graft biopsy using the Banff Classification. The histological criteria for antibody-mediated rejection (AMR) are poorly reproducible and inconsistently associated with outcome. We hypothesized that a 34-gene set associated with antibody-mediated rejection in other solid organ transplants could improve diagnosis in pancreas grafts. The AMR 34-gene set, comprising endothelial, natural killer cell and inflammatory genes, was quantified using the NanoString platform in 52 formalin-fixed, paraffin-embedded pancreas transplant biopsies from 41 patients: 15 with pure AMR or mixed rejection, 22 with T cell-mediated rejection/borderline and 15 without rejection. The AMR 34-gene set was significantly increased in pure AMR and mixed rejection (P = .001) vs no rejection. The gene set predicted histological AMR with an area under the receiver operating characteristic curve (ROC AUC) of 0.714 (P = .004). The AMR 34-gene set was the only biopsy feature significantly predictive of allograft failure in univariate analysis (P = .048). Adding gene expression to DSA and histology increased ROC AUC for the prediction of failure from 0.736 to 0.770, but this difference did not meet statistical significance. In conclusion, assessment of transcripts has the potential to improve diagnosis and outcome prediction in pancreas graft biopsies.
Date Issued
2020-11
Date Acceptance
2020-08-11
Citation
Clinical Transplantation, 2020, 34 (11), pp.1-13
ISSN
0902-0063
Publisher
John Wiley and Sons
Start Page
1
End Page
13
Journal / Book Title
Clinical Transplantation
Volume
34
Issue
11
Copyright Statement
© 2020 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in
any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
License URL
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000563766700001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Surgery
Transplantation
antibody-mediated
Banff classification
biopsy
classification systems
expression
molecular biology
rejection
RNA and
or transcript
GENE-EXPRESSION
TRANSPLANTATION
Publication Status
Published
Article Number
ARTN e14065
Date Publish Online
2020-08-17