Minor histocompatibility antigen HA-1 and HPA-5 polymorphisms in HLA-identical related bone marrow transplantation

Abstract 

The minor histocompatibility antigens (mHags), HA-1 and HPA-5, are immunogenic alloantigens shown to be responsible for graft-versus-host disease (GVHD) in HLA-identical bone marrow transplantation. Both antigens have two known alleles each, resulting in a single amino acid polymorphism. The HA-1H allele encodes histidine, whereas the HA-1R allele encodes arginine. The HPA-5b (Br^a) allele encodes lysine, whereas the HPA-5a (Br^b) encodes glutamic acid. In this study, 49 bone marrow transplant recipients and their genetically related HLA-identical donors were evaluated for the presence of HA-1, whereas 39 recipients, different from the abovementioned ones, and their HLA-identical siblings were analyzed for the presence of HPA-5. The frequencies of the two alleles of HA-1 in the recipient population were HA-1R = 0.663 and HA-1H = 0.336. In the donor population, the respective frequencies were 0.704 and 0.296. Seven donors (14.5%) were mismatched with the recipients for HA-1H. In contrast, the frequencies of the two alleles of HPA-5 in the recipient population were HPA-5a = 0.859 and HPA-5b = 0.141; whereas, among donors, they were 0.820 and 0.180, respectively. Five donors (12.8%) were found to be mismatched with their recipients for HPA-5. These results provide insight into the polymorphism of mH antigens based on the study of their frequencies in bone marrow transplant recipients and their genetically HLA-identical siblings, an endeavor that is essential to investigate the presence of HA-1 and HPA-5 mHags.