Is Allele Level Typing Necessary for

Is Allele Level Typing Necessary for Related Bone Marrow Transplantation? SA Berger, KA Hopkins, JM Hart, AA Zachary,and MS Leffell. Johns Hopkins University School of Medicine, Baltimore, MD.

Extensive HLA polymorphism necessitates allele level typing for allogenic BMT. However, the definition of new alleles has resulted in increasing numbers of typing ambiguities. Conversely, health care cost containment efforts exert continual pressure to reduce the extent of HLA typing. In 1997, we reported an alogorithm for determining the likelihood of genotypic HLA identity of siblings who were identical at the antigen level. Even in the case of parents sharing the most common haplotype in their racial group, the probability of genotypic identity between antigenically identical siblings was >99%. This prediction was confirmed in an evaluation of 394 BMT cases. In face of the number of new alleles defined, we have re-examined the outcome of allele level typing and/or genotyping in donor/recipient pairs identical at the antigen level. A total of 765 cases were reviewed in which 363 HLA-A,B identical sib pairs were identified; 265/363 (73%) and 98/363(27%) were resolved by high resolution typing and genotyping, respectively. Class I antigens were defined by serology for >95% of the samples and, for the past two years by both serology and SSP for >80%. Class II antigens and alleles were defined by reverse SSOP and SBT. Of the 363 A, B identical sib pairs, 361(99.5%) were found to be identical at the DR antigen level. 100% of those identical at the antigen level for A,B, and DR were confirmed identical for DRB1 alleles. DQB1 alleles were also determined for 265 pairs with 100% identity. In the two cases where class II identity was not confirmed, there was apparent parental sharing of two common HLA-A,B haplotypes: A1;B8 and A3;B7. These data suggest that for siblings phenotypic identity for HLA-A and B antigens confers <0.6% chance of genotypic non-identity. In contrast , for unrelated donors, identical at the antigen level in registry searches, we have found 17.5% non-identity for class I antigens and 35.9% non-identity for class II alleles upon confirmatory typing.