Even single amino acid differences between HLA proteins can have a profound effect on their ability to present antigen, interact with T lymphocytes, and stimulate allorecognition (transplant rejection or graft vs host disease).
The frequencies of specific HLA alleles and haplotypes (alleles on one chromosome) differ in different racial/ethnic groups but approximately two-thirds of the alleles and most theoretical haplotypes are rare.
HLA typing uses either DNA-based methods to define which potential alleles are carried or serology to define which proteins are expressed by an individual.
The ability of DNA-based typing to identify alleles varies depending on the method and reagents used. Typing of new volunteers for a registry is usually at low to intermediate resolution, narrowing down the potential alleles carried by an individual. Typing of a patient for transplant usually defines specific alleles carried by the patient. This is a newer method, and an increasing number of volunteer donors are typed by these methods.
Serologic typing is low resolution; it does not define which of many alleles might be carried by an individual. Large numbers of volunteer donor typings on registries were obtained with this method.
Seventy percent of patients with fatal blood diseases treated with hematopoietic stem cell transplant require an unrelated donor and are served by registry and cord blood banks around the world.
A registry/bank must possess sophisticated algorithms for storing and matching to address the complexity of HLA assignments received on volunteer donors/cord blood units. Quality control of typing is also critical.
While transplant centers differ in their definition of a “match,” the National Marrow Donor Program, has recommended matching for alleles at 4 HLA loci, HLA-A, -B, -C, -DRB1. When possible, DQB1 matching may provide additional benefit.
The average patient searching the >5 million NMDP registry has an 85 percent chance of finding a 6 of 6 antigen match. Of the 6 of 6 antigen matches undergoing transplant, the probability of finding a 6 of 6 allele match is about 72 percent, a 10 of 10 allele match is about 50 percent, and a 12 of 12 match is 11 percent. The chance of finding a 6 of 6 antigen match for minorities is lower: 65 percent for an African American patient, and probability of allele matching has not yet been evaluated.
The probability of match depends on allele and haplotype frequencies.
Registries should possess the ability to evaluate the HLA characteristics of the database to improve knowledge of the HLA system and to enhance their ability to identify suitable donors for all patients.