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ALLELE-SPECIFIC HLA ALLOANTIBODIES AND IMPLICAITONS FOR ORGAN ALLOCATION.
Robert A. Bray Ph.D. 1 and Howard M. Gebel Ph.D. 1. 1 Pathology, Emory University, Atlanta, GA, USA .
Recent advances in HLA antibody screening (ie; Microparticles coated with individual HLA molecules) have provided new tools for identifying alloantibodies in transplant patients including the ability to detect allele-specific alloantibodies. In this study, we report on 6 individuals whose HLA alloantibody was restricted to a unique HLA allele or group of alleles (Table). For 3 patients, an allele-specific antibody was observed following failure of a
DR antigen matched
renal allograft. Two patients made antibodies following blood transfusions and one patient
s antibody resulted from pregnancy.
Table 1 Pt. ID Pt. HLA Type Donor HLA Type Alloantibody Detected 1 DRB1*0101 DRB1*0103 DRB1*0103 2 DRB1*0405 DRB1*0401 DRB1*0401, *0404, *0408 3 DRB1*0801 DRB1*0803 DRB1*0803 4 DRB1*0802 Unknown DRB1*0801, *0803, *1303, *1313 5 A*6802 A*6801 A*6801 6 B*0801, B*4001 Unknown B*2702
Assessment of the protein sequences showed that these antibodies recognized unique epitopes at predominantly antibody accessible sites. While the importance of allelic differences is well known in stem cell transplantation, their significance in solid organ transplantation has not been studied. High-resolution typing is not currently performed for solid organ transplantation but for selected highly-sensitized patients, the failure to discriminate allele-specific from antigen-specific antibodies can limit access to acceptable organs. We believe that our observations have important implications in renal allograft allocation. Specifically, among highly sensitized patients, the identification of allele-specific antibodies will be necessary to correctly predict a negative crossmatch.