HLAMatchmaker is a new algorithm to determine HLA compatibility at the structural level. Donorrecipient HLA matching is assessed by intralocus and interlocus comparisons of polymorphic amino acid tdplet sequences in alloantibody-accessible positions of HLA molecules. For many patients, HLAMatchmaker can identify mismatched HLA antigens that are zero-triplet mismatches and should therefore, be considered fully histocompatible at the structural level. Recent studies have shown that HLA class I triplet matching correlates with excellent kidney transplant outcome and that HLAMatchmaker provides a useful strategy to identify more compatible donors. After working with the various HLAMatchmaker programs downloaded from our website, many HLA professionals share our belief that this algorithm is superior to the conventional HLA matching system especially for sensitized patients as well as minority groups for whom it is often difficult to find compatible donors. This project deals with studies on refining and expanding the HLAMatchmaker algorithm and how this program can be used in a clinical setting. There are four objectives: (1) Study the serological identification of triplet-defined of epitopes recognized by human monoclonal alloantibodies, (2) Determine the relative immunogenicity of triplet-defined epitopes, (3) Assess clinical relevance of HLAMatchmaker in platelet transfusion support of refractory thrombocytopenic patients and stem cell transplantation from unrelated donors, (4) Apply HLAMatchmaker for determining the structural basis of HLA class II compatibility. These studies will increase our understanding of the structural basis of HLA compatibility. The ultimate goal of this project is the application of HLAMatchmaker as a new donor selection strategy in transplantation and platelet transfusions nationwide

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI055933-04
Application #
7002292
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Program Officer
Macchiarini, Francesca
Project Start
2003-09-15
Project End
2007-12-31
Budget Start
2006-01-01
Budget End
2006-12-31
Support Year
4
Fiscal Year
2006
Total Cost
$310,900
Indirect Cost
Name
University of Pittsburgh
Department
Pathology
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Marrari, Marilyn; Duquesnoy, Rene J (2010) Detection of donor-specific HLA antibodies before and after removal of a rejected kidney transplant. Transpl Immunol 22:105-9
Duquesnoy, R J; Marrari, M (2009) Correlations between Terasaki's HLA class I epitopes and HLAMatchmaker-defined eplets on HLA-A, -B and -C antigens. Tissue Antigens 74:117-33
Duquesnoy, Rene J; Marrari, Marilyn (2009) HLAMatchmaker-based definition of structural human leukocyte antigen epitopes detected by alloantibodies. Curr Opin Organ Transplant 14:403-9
Marrari, Marilyn; Duquesnoy, Rene J (2009) Why can sensitization by an HLA-DR2 mismatch lead to antibodies that react also with HLA-DR1? Hum Immunol 70:403-9
Marrari, M; Duquesnoy, R J (2009) Correlations between Terasaki's HLA class II epitopes and HLAMatchmaker-defined eplets on HLA-DR and -DQ antigens. Tissue Antigens 74:134-46
Duquesnoy, Rene J; Awadalla, Yehia; Lomago, Jon et al. (2008) Retransplant candidates have donor-specific antibodies that react with structurally defined HLA-DR,DQ,DP epitopes. Transpl Immunol 18:352-60
Duquesnoy, Rene; Spellman, Stephen; Haagenson, Michael et al. (2008) HLAMatchmaker-defined triplet matching is not associated with better survival rates of patients with class I HLA allele mismatched hematopoietic cell transplants from unrelated donors. Biol Blood Marrow Transplant 14:1064-71
Duquesnoy, Rene J; Mostecki, Justin; Hariharan, Jayasree et al. (2008) Structurally based epitope analysis of major histocompatibility complex class I-related chain A (MICA) antibody specificity patterns. Hum Immunol 69:826-32
Duquesnoy, Rene J (2008) Clinical usefulness of HLAMatchmaker in HLA epitope matching for organ transplantation. Curr Opin Immunol 20:594-601
Duquesnoy, Rene J (2008) Structural epitope matching for HLA-alloimmunized thrombocytopenic patients: a new strategy to provide more effective platelet transfusion support? Transfusion 48:221-7

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