The allelic diversity and associated human leukocyte antigen (HLA) disparity of 1775 bone marrow recipients and their unrelated donors, matched for six of six (1361/1775,77%), five of six (397/1775, 22%), or four of six (17/1775, 1%) HLA-A, -B, -DR antigens, were retrospectively evaluated. The comprehensive HLA analysis included the class I (A, B, C) and II (DRB1, DQA1, DQB1, DPA1, DPB1) loci. Most (>66%) of the predominantly Caucasian study population carried one or two of five to seven common alleles at each HLA locus. In spite of this limited diversity, 29% of the six of six antigen-matched transplants carried allele mismatches at HLA-A, -B, and/or -DRB1, and 92% carried at least one allele mismatch at one of the eight HLA loci tested. Of the 968 HLA-A,-B,-DRB1 allele-matched pairs, 89% carried mismatches at other HLA loci, predominantly at DP loci. The substantially greater than expected HLA allelic disparity between donor and recipient suggests extensive haplotypic diversity and underscores the importance of enhancing approaches to mitigate the deleterious effect of HLA mismatches.
Bibliographical noteFunding Information:
This work was supported by funding from the Office of Naval Research (N00014-93-1-0658, N00014-95-1-0055, N00014-96-2-0016) and Health Resources and Services Administration (240-97-0036), (National Marrow Donor Program) and the Office of Naval Research (N00014-94-1-0049, N00014-99-1-0551), (C. K. Hurley Research Program). We would like to acknowledge the assistance of the NMDP transplant and donor centers in providing cells and data for this study, Delene Johnson and her staff at the Blood Centers of the Pacific-Irwin Center for providing repository samples for analysis, the technical staff at the HLA typing laboratories, past participants in this retrospective study, and NMDP personnel including Michael Diko, Rose Fritz, Kenneth Bengtsson, Martin Maiers, and Penny Sinner for their assistance with the HLA typing and data analysis. Assistance with the design of the study was provided by Bo Dupont and helpful comments were provided by the NMDP Histocompatibility Committee.
- Bone marrow transplantation