Open Access
Molecular‐level HLA mismatch is associated with rejection and worsened graft survival in heart transplant recipients – a retrospective study
Author(s) -
OsorioJaramillo Emilio,
Haasnoot Geert W.,
Kaider Alexandra,
Schaefer AnneKristin,
Haberl Thomas,
Goekler Johannes,
Angleitner Philipp,
Moayedifar Roxana,
Zuckermann Andreas,
Fischer Gottfried F.,
Laufer Guenther,
Claas Frans H. J.,
AliabadiZuckermann Arezu Z.
Publication year - 2020
Publication title -
transplant international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.998
H-Index - 82
eISSN - 1432-2277
pISSN - 0934-0874
DOI - 10.1111/tri.13657
Subject(s) - medicine , human leukocyte antigen , hazard ratio , heart transplantation , confidence interval , transplantation , histocompatibility testing , panel reactive antibody , retrospective cohort study , proportional hazards model , hla dq , serology , immunology , antigen , gastroenterology , antibody , allele , haplotype , biochemistry , chemistry , gene
Abstract 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.