A comprehensive analysis of the HLA-D region loci, DRB1, DRB3, DRB5, DQA1, DQB1, DPA1 and DPB1, was performed to determine allelic diversity and underlying HLA disparity in 1259 bone marrow recipients and their unrelated donors transplanted through the National Marrow Donor Program. Although 43.0% of DRB1 alleles known to exist at the beginning of the study were found in this predominantly Caucasian transplant population, a few alleles predominated at each locus. In recipients, 67.1% of DRB1 alleles identified were one or two of six common DRB1 alleles. Only 118 (9.4%) donor-recipient pairs were matched for all alleles of DRB1, DQA1, DQB1, DPA1 and DPB1. While 79.4% of the pairs were matched for DRB1, only 13.2% were matched for DPB1 alleles. Almost 66% of pairs differed by more than one allele mismatch and 59.0% differed at more than one HLA-D locus. DQB1 was matched in 85.9% of DRB1-matched pairs. In contrast, only 13.9% of the pairs matched for DRB1, DQA1 and DQB1 were also matched for DPA1 and DPB1. This database, highlighting the underlying HLA disparity within the pairs, forms the foundation of an ongoing study to establish the relationship between HLA matching and successful outcome in unrelated allogeneic stem cell transplant.
Bibliographical noteFunding Information:
This research has been supported by funding from the Office of Naval Research N00014–93–1-0658 to National Marrow Donor Program and N00014–92-J-4036 and N00014–94–1-0049 to the CW Bill Young Marrow Donor Recruitment and Research Program. The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, the Department of Defense, or the US government. We would like to acknowledge the assistance of the NMDP Transplant and Donors Centers in providing cells and data for this study, the DNA-based registry typing laboratories for their assistance in determining the preliminary DRB and DQB1 typing of the samples, and our laboratory staff and NMDP personnel for their assistance with the HLA typing and data analysis. Dr Bo Dupont was instrumental in the original design of this project and oversight was provided by the NMDP Histocompatibility Committee. This manuscript is dedicated to the memory of our friend and colleague, Michael Chopek, MD. Dr Chopek participated in the early phases of the design, data collection and analysis of this project. His enthusiasm and commitment have inspired us and we are saddened that he was unable to see this work come to fruition.
- Bone marrow transplantation
- HLA matching