HLA Amino Acid Polymorphisms and Kidney Allograft Survival
| Autor: | Keith McCullough, Robert M. Merion, Valerie Teal, Marcelo A. Fernandez Viña, Martin Maiers, Hongzhe Li, Alan B. Leichtman, Malek Kamoun |
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| Rok vydání: | 2017 |
| Předmět: |
Genetic Markers
Graft Rejection 0301 basic medicine Graft failure Human leukocyte antigen 030230 surgery Antigen recognition site 03 medical and health sciences 0302 clinical medicine Text mining Hla molecules HLA Antigens Allograft survival Humans Medicine Proportional Hazards Models chemistry.chemical_classification Transplantation Kidney Polymorphism Genetic business.industry fungi Graft Survival Original Clinical Science—General Kidney Transplantation Amino acid 030104 developmental biology medicine.anatomical_structure chemistry Immunology Linear Models business Follow-Up Studies |
| Zdroj: | Transplantation |
| ISSN: | 0041-1337 |
| Popis: | Background The association of HLA mismatching with kidney allograft survival has been well established. We examined whether amino acid (AA) mismatches (MMs) at the antigen recognition site of HLA molecules represent independent and incremental risk factors for kidney graft failure (GF) beyond those MMs assessed at the antigenic (2-digit) specificity. Methods Data on 240 024 kidney transplants performed between 1987 and 2009 were obtained from the Scientific Registry of Transplant Recipients. We imputed HLA-A, -B, and -DRB1 alleles and corresponding AA polymorphisms from antigenic specificity through the application of statistical and population genetics inferences. GF risk was evaluated using Cox proportional-hazards regression models adjusted for covariates including patient and donor risk factors and HLA antigen MMs. Results We show that estimated AA MMs at particular positions in the peptide-binding pockets of HLA-DRB1 molecule account for a significant incremental risk that was independent of the well-known association of HLA antigen MMs with graft survival. A statistically significant linear relationship between the estimated number of AA MMs and risk of GF was observed for HLA-DRB1 in deceased donor and living donor transplants. This relationship was strongest during the first 12 months after transplantation (hazard ratio, 1.30 per 15 DRB1 AA MM; P < 0.0001). Conclusions This study shows that independent of the well-known association of HLA antigen (2-digit specificity) MMs with kidney graft survival, estimated AA MMs at peptide-binding sites of the HLA-DRB1 molecule account for an important incremental risk of GF. In a population of 240 024 kidney transplant recipients using the data of the Scientific Registry of Transplant recipients, the authors demonstrate that, independently of HLA antigen mismatches, estimated amino-acid mismatches at peptide-binding sites of the HLA-DRB1 molecule, accounts for an increased graft failure risk. Supplemental digital content is available in the text. |
| Databáze: | OpenAIRE |
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