Impact of HLA Diversity on Donor Selection in Organ and Stem Cell Transplantation

Abstract

The human major histocompatibility complex is a multigene system encoding polymorphic human leucocyte antigens (HLA) that present peptides derived from pathogens to the immune system. The high diversity of HLA alleles and haplotypes in the worldwide populations represents a major barrier to organ and allogeneic hematopoietic stem cell transplantation, because HLA incompatibilities are efficiently recognized by T and B lymphocytes. In organ transplantation, pre-transplant anti-HLA antibodies need to be taken into account for organ allocation. Although HLA-incompatible transplants can be performed thanks to immunosuppressive drugs, the de novo production of anti-HLA antibodies still represents a major cause of graft failure. The HLAMatchmaker computer algorithm determines the immunogenicity of HLA mismatches and allows to define HLA antigens that will not induce an antibody response. Because of the much higher stringency of HLA compatibility criteria in stem cell transplantation, the best donor is a HLA genotypically identical sibling. However, more than 50% of the transplants are now performed with hematopoietic stem cells from volunteer donors selected from the international registry. The development of European national registries covering populations with different HLA haplotype frequencies is essential for optimizing donor search algorithms and providing the best chance for European patients to find a fully compatible donor.

Targeting Innate-Like T Cells in Tuberculosis

“…The HLA gene complex is highly diverse, with more than 3,000 variant alleles discovered in the HLA-A, B, or C loci, to date, in human populations, and it can also form 15,000–70,000 possible α and β chain combinations for HLA-DQ, DR, and DP molecules (from the IMGT/HLA website: , September 13, 2016). This profound heterogeneity confers hypervariable interaction in antigen presentation for conventional T cell activation in human populations and is also functionally reflected in the difficulty of finding non-rejected graft donors for organ transplantation except for identical twins (99). …”

The HLA‐net GENE[RATE] pipeline for effective HLA data analysis and its application to 145 population samples from Europe and neighbouring areas

“…The search for compatible donors in bone marrow transplantation is a main health issue, and the impact of diversity deserves special attention . The observation of substantial HLA genetic variation at the regional level in Europe and surrounding areas indicates that some allelic combinations, including rare phenotypes, may not be found with a similar probability in all these populations.…”

HLA‐A, ‐B, ‐C, ‐DRB1, and ‐DQB1 allele and haplotype frequencies: An analysis of umbilical cord blood units at the Barcelona Cord Blood Bank

“…HLA genes are highly polymorphic 1,2 and as such are involved in allogeneic immune responses following hematopoietic stem cell transplantation (HSCT), where they play an important role in graft-vs-host disease (GVHD). 3 Studies have shown that donor-recipient HLA mismatch is significantly associated with worse survival outcomes. [4][5][6][7] Around 35 000 units of umbilical cord blood (CB) have been transplanted worldwide since the first successful transplant in 1988.…”