HLA Molecular Mismatch is an Independent Correlate of T-Cell Mediated Rejection and Potential Prognostic Biomarker in Renal Transplantation
1Medicine and Immunology, University of Manitoba, Winnipeg, MB, Canada, 2Shared Health Services, Winnipeg, MB, Canada, 3Pathology, University of Manitoba, Winnipeg, MB, Canada, 4Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, Canada, 5Medicine, University of Manitoba, Winnipeg, MB, Canada
Meeting: 2020 American Transplant Congress
Abstract number: 529
Keywords: HLA matching, Immunogenicity, MHC class II, Rejection
Session Information
Session Name: Biomarkers, Immune Assessment and Clinical Outcomes V
Session Type: Oral Abstract Session
Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:45pm
Presentation Time: 3:51pm-4:03pm
Location: Virtual
*Purpose: HLA molecular mismatch alloimmune risk categorization has correlated with de novo donor-specific antibody (dnDSA) development, however, correlation with T-cell mediated rejection (TCMR) phenotypes is not well understood.
*Methods: Using published thresholds 803 recipients were categorized into low, intermediate, or high alloimmune risk based on their HLA-DR/DQ molecular mismatch.
*Results: Alloimmune risk category correlated with Borderline (p=0.01), Banff ≥1A (p<0.01), and Banff ≥1B (p<0.01) TCMR free survival. In repeat biopsies the alloimmune risk category correlated with the mean number of Borderline (0.30, 0.49, 0.59, p=0.005) and Banff ≥1A (0.49, 0.76, 0.97, p<0.0001) rejection episodes per recipient. Alloimmune risk category was an independent multivariate correlate of borderline TCMR (HR 2.87, p<0.01) and Banff ≥1A TCMR (HR 3.12, p<0.01) after adjustment for baseline immunosuppression, delayed graft function, and recipient age.
*Conclusions: The correlation of HLA-DR/DQ molecular mismatch with borderline TCMR free survival and recurrent borderline TCMR provides evidence for the alloimmune basis of borderline rejection. HLA molecular mismatch is available at the time of transplant and may be a prognostic biomarker of both dnDSA and TCMR free survival post-transplant for use in precision medicine risk stratification or enrichment in clinical trial design.
To cite this abstract in AMA style:
Wiebe C, Pochinco D, Gibson IW, Ho J, Birk P, Goldberg A, Karpinski M, Shaw J, David RN, Nickerson PW. HLA Molecular Mismatch is an Independent Correlate of T-Cell Mediated Rejection and Potential Prognostic Biomarker in Renal Transplantation [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/hla-molecular-mismatch-is-an-independent-correlate-of-t-cell-mediated-rejection-and-potential-prognostic-biomarker-in-renal-transplantation/. Accessed November 21, 2024.« Back to 2020 American Transplant Congress