Key result
A higher HLA-DR amino acid mismatch load was associated with inferior 1-year graft survival (HR 1.14; 95% CI 1.01-1.28) in primary heart transplant recipients.
Why the study?
The study was conducted to evaluate the association of molecular-level human leukocyte antigen mismatching with post-transplant graft survival, rejection, and cardiac allograft vasculopathy.
Does a higher molecular-level HLA mismatch load worsen graft survival and increase rejection in heart transplant recipients?
Cohort (n=1,167)
Does a higher molecular-level HLA mismatch load worsen graft survival and increase rejection in heart transplant recipients?
Hazard Ratio: 1.14 (95% CI 1.01–1.28)
Higher molecular-level HLA-DR mismatch load is associated with inferior 1-year graft survival and increased risk of rejection in heart transplant recipients, suggesting its potential utility for risk stratification.
Higher HLA-DR epitope mismatch load was associated with inferior graft survival; leaves open whether molecular matching refines risk stratification in heart transplantation.
The aim was to evaluate the association of molecular-level human leukocyte antigen (HLA) mismatching with post-transplant graft survival, rejection, and cardiac allograft vasculopathy (CAV). We retrospectively analyzed all primary cardiac transplant recipients between 01/1984-06/2016. 1167 patients fulfilled inclusion criteria and had HLA typing information available. In 312 donor-recipient pairs, typing at serological split antigen level was available. We used the Epitope MisMatch Algorithm to calculate the number of amino acid differences in antibody-verified HLA eplets (amino acid mismatch load (AAMM)) between donor and recipient. Patients with a higher HLA-DR AAMM load had inferior 1-year graft survival (hazard ratio [HR], 1.14; 95% confidence interval [CI], 1.01-1.28). The HLA-AB AAMM load showed no impact on graft survival. In the subgroup with available split-level information, we observed an inferior graft survival for a higher HLA-DR AAMM load 3 months after transplantation (HR, 1.22; 95% CI, 1.04-1.44) and a higher risk for rejection for an increasing HLA-AB (HR, 1.70; 95% CI, 1.29-2.24) and HLA-DR (HR, 1.32; 95% CI, 1.09-1.61) AAMM load. No impact on the development of CAV was found. Molecular-level HLA mismatch analysis could serve as a tool for risk stratification after heart transplantation and might take us one step further into precision medicine.
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Osorio‐Jaramillo et al. (2020) conducted a cohort in Primary cardiac transplant recipients (n=1,167). Higher HLA-DR amino acid mismatch load vs. Lower HLA-DR amino acid mismatch load was evaluated on 1-year graft survival (HR 1.14, 95% CI 1.01-1.28). A higher HLA-DR amino acid mismatch load was associated with inferior 1-year graft survival (HR 1.14; 95% CI 1.01-1.28) in primary heart transplant recipients.
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