Shedding a new light on the HLA matching

which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The first human bone marrow transplantation in a patient with hematologic malignancy took place in the 1950s, but only transient engraftment of the bone marrow was noted [1]. In the 1960s, additional information regarding the HLA system became available; the serologic HLA typing method was developed; and bone marrow transplantations for children with immnunodeficiency were successfully performed [2]. Hematopoietic stem cell transplantation (HSCT) has now become an established and potentially curative treatment modality for many malignant and nonmalignant diseases affecting the hematopoietic and immune systems. However, only approximately 30% of the patients requiring HSCT have an HLA-matched sibling donor; the remaining 70% need to find alternative sources of hematopoietic stem cells (HSCs), such as an HLA-mismatched related donor, a closely HLA-matched unrelated donor (URD), or umbilical cord blood. The alloantigens differing between donors and recipients become targets for T-cell recognition. Hence, large numbers of genetic differences between donors and recipients increase the risk of both graft rejection and graft-versus-host disease (GVHD); the graft-versus-tumor effect may be beneficial. Therefore, the most important determinant of successful allogeneic HSCT is the degree of HLA matching between the donor and recipient. HLAs are alloantigens and cell surface molecules encoded by class I (HLA-A, HLA-B, and HLA-C) and class II (HLA-DR, HLA-DP, and HLA-DQ) genes, which are a series of closely linked loci known as the major histocompatibility complex (MHC) that are located on chromosome 6 (6p21.3) in humans [3]. Historically, HLA typing was conducted by serologic testing by using antiserum in complement-dependent cytotoxic assays. Recently, more precise DNA-based HLA typing methods using molecular techniques, such as sequence-specific oligonucleotide probe hybridization, sequence-specific primer amplification, sequencing-based typing, and reference strand-based conformation analysis, have been developed and are frequently used. HLA are highly poly-morphic, and gene sequencing analysis has revealed more than 800 HLA alleles. The current standard is HLA typing at the HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 genetic loci. An HSCT donor is referred to as a " 10/10 allele match " or " perfect match " when both HLA alleles are identical at each of the HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 loci. While searching for an unrelated donor, high-resolution (4-digit) genetic typing of both the patient and the donor is necessary [4, 5]. In cases of perfect match, minor histocompatibility anti-gens, which are naturally processed …