Computer analysis of Human Leukocyte Antigen (HLA) phenotypes from over 100,000 transplants can identify dominant Major Histocompatibility Complex (MHC) epitopes. The first phase of this project was initiated over eight years ago with a computer program that converted donor and recipient HLA antigens to their amino acid sequences. Ten critical epitopes were identified that correlated with fewer rejection episodes and improved graft outcome. Projections in two racially diverse pools indicated that epitope matching would increase the number of compatible transplants and improve racial equity. Prospective kidney allocation to avoid mismatches of these epitopes was initiated in 1995. The second phase of this project will include a multivariate analysis to determine the relative affects of recipient race, donor age, modern immunosuppression regimens and epitope match on graft outcome. A comparison of recipient selection and crossmatch results before and after initiation of the protocol will demonstrate the impact of epitope matching on racial equity. The contribution of each epitope to positive crossmatches, rejection episodes and graft failure will be individually re-evaluated to determine optimal epitopes for the matching algorithm. The possibility of improving the algorithm by considering different sets of epitopes depending on the race of the recipient will also be examined. The third phase of this research, inclusion of these epitopes in the national kidney allocation protocol, may begin as early as this year. Significance of this research applies to all fields of transplantation where MHC matching has an influence on graft outcome.
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