%0 Journal Article
%T Role of HLA in Hematopoietic Stem Cell Transplantation
%A Meerim Park
%A Jong Jin Seo
%J Bone Marrow Research
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/680841
%X The selection of hematopoietic stem cell transplantation (HSCT) donors includes a rigorous assessment of the availability and human leukocyte antigen (HLA) match status of donors. HLA plays a critical role in HSCT, but its involvement in HSCT is constantly in flux because of changing technologies and variations in clinical transplantation results. The increased availability of HSCT through the use of HLA-mismatched related and unrelated donors is feasible with a more complete understanding of permissible HLA mismatches and the role of killer-cell immunoglobulin-like receptor (KIR) genes in HSCT. The influence of nongenetic factors on the tolerability of HLA mismatching has recently become evident, demonstrating a need for the integration of both genetic and nongenetic variables in donor selection. 1. Introduction Allogeneic hematopoietic stem cell transplantation (HSCT) has been established as a mode of curative therapy for hematologic malignancies and other hematologic or immune disorders. Hematopoietic stem cell donor selection has been almost exclusively based on selecting an human leukocyte antigen (HLA) identical donor or near-identical donor; however, not all patients are able to find a suitable donor. Advances in HLA testing and matching and understanding donor selection factors are therefore important to improve outcomes of unrelated donor (UD) HSCT. HLAs can elicit an immune response either by presentation of variable peptides or by recognition of polymorphic fragments of foreign HLA molecules. HLA disparity has been associated with graft failure, delayed immune reconstitution, graft-versus-host disease (GVHD), and mortality. Since many patients lack HLA-matched donors, current research is focused on the identifying permissible HLA mismatches. Recently, extensive research has accumulated evidence on the role of each HLA locus mismatch on clinical outcome for UD HSCT, making it easy to search for and select a partially matched donor [1, 2]. In this paper, we will focus on the current understanding of HLA typing and its clinical implications on UD HSCT. 2. HLA Typing HLA class I and II loci are the most polymorphic genes in the human genome, with a highly clustered and patchwork pattern of sequence motifs [3]. Each individual carries 10 to 12 genes that encode the HLA-A, -B, -C, -DR, -DQ, and -DP. Most of these genes are highly polymorphic, ranging from 13 (HLA-DRB4) to 699 (HLA-B) alleles per locus [4]. Extensive allelic diversity has made, and continues to make, high-resolution HLA-DNA typing very challenging. Over the past three decades, the
%U http://www.hindawi.com/journals/bmr/2012/680841/