Advances in HLA: Practical Implications for Selecting Adult Donors and Cord Blood Units

Abstract

HLA plays a critical role in hematopoietic cell ransplantation, but a full understanding of this role is onstantly in flux because of changing technologies nd burgeoning amounts of clinical transplantation esults. Today the clinician considering unrelated donor ransplantation must also consider stem cell source: an dult donor or an umbilical cord blood unit (CBU). In he context of cord blood, the task is further compliated by the strong interaction of cell dose. Each individual carries from 10 to 12 genes that ncode the HLA-A, HLA-B, HLA-C, HLA-DR, HLAQ, and HLA-DP molecules. Most of these genes are ighly polymorphic, ranging from 13 (HLA-DRB4) to 99 (HLA-B) alleles at a locus [1]. Most of the allelic ifferences result in changes in the HLA protein seuences, thus producing potential targets for allorecogition [2]. The frequency of alleles differs in different opulations: some are common in most populations, nd others are found predominantly in only 1 or a few opulations. The same is true for HLA haplotypes—the ollection of multiple HLA alleles within a short reion of chromosome 6—which are typically inherited s a single block of genetic information. Table 1 proides examples. DNA-based testing methods provide an accurate nd powerful approach to identify HLA diversity, and hese are replacing serologic testing [3,4]. DNA testng detects specific nucleotide differences that distinuish alleles or sets of alleles. The ability to distinuish among particular alleles at a locus (ie, the esolution) depends on the methodology, the set of ligonucleotide reagents used in the assay, or both. he choice of assay depends on the purpose of the yping, eg, initial testing of newly recruited volunteers r CBUs for a registry (low to intermediate resoluion) compared with testing of transplantation candiates and a few selected potential donors or CBUs high or allele-level resolution). C