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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK054928-01
Application #
2740964
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1998-09-01
Project End
2003-06-30
Budget Start
1998-09-01
Budget End
1999-06-30
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Surgery
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Wade, Judith A; Hurley, Carolyn Katovich; Takemoto, Steven K et al. (2007) HLA mismatching within or outside of cross-reactive groups (CREGs) is associated with similar outcomes after unrelated hematopoietic stem cell transplantation. Blood 109:4064-70
Bunnapradist, S; Takemoto, S K (2003) Controlling treatment allocation bias in a registry analysis when comparing calcineurin inhibitors. Transplant Proc 35:2407-8
Duquesnoy, Rene J; Howe, Judy; Takemoto, Steve (2003) HLAmatchmaker: a molecularly based algorithm for histocompatibility determination. IV. An alternative strategy to increase the number of compatible donors for highly sensitized patients. Transplantation 75:889-97
Duquesnoy, Rene J; Takemoto, Steve; de Lange, Peter et al. (2003) HLAmatchmaker: a molecularly based algorithm for histocompatibility determination. III. Effect of matching at the HLA-A,B amino acid triplet level on kidney transplant survival. Transplantation 75:884-9
Bunnapradist, Suphamai; Daswani, Adarsh; Takemoto, Steven K (2003) Graft survival following living-donor renal transplantation: a comparison of tacrolimus and cyclosporine microemulsion with mycophenolate mofetil and steroids. Transplantation 76:10-5
Takemoto, S (2002) Patterns and outcomes for maintenance immunosuppression in the UNOS renal transplant registry. Transplant Proc 34:1632-4
Tambur, A R; Bray, R A; Takemoto, S K et al. (2000) Flow cytometric detection of HLA-specific antibodies as a predictor of heart allograft rejection. Transplantation 70:1055-9
McKenna, R M; Takemoto, S K; Terasaki, P I (2000) Anti-HLA antibodies after solid organ transplantation. Transplantation 69:319-26
Takemoto, S K; Terasaki, P I; Gjertson, D W et al. (2000) Twelve years' experience with national sharing of HLA-matched cadaveric kidneys for transplantation. N Engl J Med 343:1078-84
Takemoto, S K; Cho, Y W; Gjertson, D W (1999) Transplant risks. Clin Transpl :325-34

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