#48
DEFINITION OF THE HLA POPULATION DIVERSITY BOUNDARIES FOR CLINICAL HISTOCOMPATIBILITY PRACTICE.
Marcelo Fernandez-Vina Ph.D. 1 and Pedro Cano 1. 1 Laboratory Medicine, M.D. Anderson Cancer Center, Houston, TX, USA .
Reliable HLA allele frequencies are essential in the development and selection of molecular typing methods, and are important in allogeneic bone-marrow transplantation to determine the likelihood of finding HLA matched donors. Only 69 HLA-A, 162 B, 42 Cw, 82 DRB1, 25 DRB3/4/5, 23 DQB1, and 41 DPB1 alleles were identified in more than 22,000 subjects, including some only present in isolated and small ethnic groups, and 10-20% fortuitous alleles, found only once. We observed only a fraction of all the alleles so far described. The number of alleles of loci whose products are highly expressed in the cell surface (A, B, C and DRB1) was higher than those found for the loci with low cell surface expression (DRB3/4/5, DQB1 and DPB1). A smaller percentage of described alleles were actually observed for HLA-A, B, C and DRB1 compared to the less polymorphic loci. The catalogue of HLA alleles must distinguish well-documented alleles comprising the polymorphic HLA universe, from the nebulous set of sporadic alleles found only once. This distinction is a useful tool in routine histocompatibility practice, as decisions about addition of tests needed to resolve ambiguous assignments are made, and unnecessary tests for the resolution of ambiguities including poorly documented alleles are prevented. It is also valuable in the design of HLA typing strategies; for example development of reagents for typing DQB1 and DRB3/4/5 should focus to resolve unambiguous genotypes including the 23 and 25 alleles identified in this study at these loci. The 20 DPB1 alleles cover more than 99% of the alleles of this locus, and methods to test for the presence of antibodies in the patient
s serum against these alleles may turn out to be highly informative to predict risks for rejection.