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IDENTIFICATION OF ALLELE-SPECIFIC HLA CLASS II ALLOANTIBODIES: PARADIGM OR PARADOX.
Robert A. Bray, Ph.D., Lisa Wilmoth-Hosey, B.S., Pam Chapman, B.S., Joan E. Holcomb, M.S. and Howard M. Gebel, Ph.D. Atlanta GA, USA, Emory University Hospital, 30322, Pathology.
Recent advances in microparticle technology have provided new tools for the detailed assessment of HLA alloantibodies including the ability to resolve allele-specific antibodies. In this study, we identified 4 individuals whose Class II alloantibody responses were each restricted to a unique epitope expressed on a distinct HLA allele or group of alleles (see table). Interestingly, for 3 of 4 patients this antibody response was observed following the failure of a “DR antigen matched” renal allograft. The 4th patient’s antibody resulted from blood transfusion.
Patient Pt. HLA Type Donor HLA 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
Comparison of the protein sequences of the alleles recognized by these antibodies revealed that, in each instance, the response appeared to be directed against a unique epitope. While the importance of allelic differences is well recognized in stem cell transplantation, their significance in solid organ transplantation has not been investigated. We believe that our observations may have important implications in renal allograft allocation. Specifically, among highly sensitized patients, the identification of allele-specific antibodies may be necessary to correctly predict a negative crossmatch. Additionally, allele-level typing of donors and sensitized recipients may also be required. In conclusion, our results show that even in the context of a “DR antigen matched” allograft, significant immunologic differences still exist.