Affordable Access

deepdyve-link
Publisher Website

Evidence for the alloimmune basis and prognostic significance of Borderline T cell-mediated rejection.

Authors
  • Wiebe, Chris1, 2, 3
  • Rush, David N1
  • Gibson, Ian W2, 4
  • Pochinco, Denise2
  • Birk, Patricia E5
  • Goldberg, Aviva5
  • Blydt-Hansen, Tom6
  • Karpinski, Martin1
  • Shaw, Jamie1
  • Ho, Julie1, 3
  • Nickerson, Peter W1, 2, 3
  • 1 Department of Medicine, University of Manitoba, Winnipeg, Canada. , (Canada)
  • 2 Shared Health Services Manitoba, Winnipeg, Canada. , (Canada)
  • 3 Department of Immunology, University of Manitoba, Winnipeg, Canada. , (Canada)
  • 4 Department of Pathology, University of Manitoba, Winnipeg, Canada. , (Canada)
  • 5 Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Canada. , (Canada)
  • 6 Department of Pediatrics, University of British Columbia, Winnipeg, Canada. , (Canada)
Type
Published Article
Journal
American Journal of Transplantation
Publisher
Wiley (Blackwell Publishing)
Publication Date
Sep 01, 2020
Volume
20
Issue
9
Pages
2499–2508
Identifiers
DOI: 10.1111/ajt.15860
PMID: 32185878
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Prognostic biomarkers of T cell-mediated rejection (TCMR) have not been adequately studied in the modern era. We evaluated 803 renal transplant recipients and correlated HLA-DR/DQ molecular mismatch alloimmune risk categories (low, intermediate, high) with the severity, frequency, and persistence of TCMR. Allograft survival was reduced in recipients with Banff Borderline (hazard ratio [HR] 2.4, P = .003) and Banff ≥ IA TCMR (HR 4.3, P < .0001) including a subset who never developed de novo donor-specific antibodies (P = .002). HLA-DR/DQ molecular mismatch alloimmune risk categories were multivariate correlates of Banff Borderline and Banff ≥ IA TCMR and correlated with the severity and frequency of rejection episodes. Recipient age, HLA-DR/DQ molecular mismatch category, and cyclosporin vs tacrolimus immunosuppression were independent correlates of Banff Borderline and Banff ≥ IA TCMR. In the subset treated with tacrolimus (720/803) recipient age, HLA-DR/DQ molecular mismatch category, and tacrolimus coefficient of variation were independent correlates of TCMR. The correlation of HLA-DR/DQ molecular mismatch category with TCMR, including Borderline, provides evidence for their alloimmune basis. HLA-DR/DQ molecular mismatch may represent a precise prognostic biomarker that can be applied to tailor immunosuppression or design clinical trials based on individual patient risk. © 2020 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.

Report this publication

Statistics

Seen <100 times