HLA-B44 SUBTYPES AND THE CHANCE OF FINDING HLA COMPATIBLE DONOR RECIPIENT PAIRS FOR BONE-MARROW TRANSPLANTATION - A HAPLOTYPE STUDY OF 303 ITALIAN FAMILIES/

A total of 1176 HLA-A,B,DR haplotypes were reconstructed by typing 303 unrelated families referred to our laboratory during the last seven y ears for the search of HLA identical sibs in view of bone marrow trans plantation. A total of 614 different three-locus haplotypes were found . Most of them (83.6%) were present only once or twice, whereas 24/614 (3.9%) were found 6-28 times each. HLA-B44 was present in 4 of these most frequent haplotypes. HLA-B44 has been implicated as the molecular target for bone marrow allograft rejection. Therefore, a better knowl edge of the HLA-B44 haplotype relationships might prove useful for the programming of registries of unrelated bone marrow donors. Eighty fiv e serologically defined HLA-B44 unrelated subjects, either one or both parents from the above families, were subtyped by a high-resolution s equence-specific oligonucleotide probing approach. Moreover, 34 unrela ted potential donors recruited for those patients that did not find a suitable donor among their siblings were subtyped also for HLA-B44. B 4403, which accounted for 47/85 (55.3%) serologically defined B44 alle les, appeared in strong, statistically significant, linkage disequilib rium with HLA-A29, -A23 and -DR7. On the other hand, B4402, which cov ered virtually all other B44 alleles, showed prevalent gametic associa tions with HLA-A2 and HLA-A24. The linkage disequilibrium between HLA alleles is the key for the low frequency of HLA-B44 mismatches in dono rs selected as HLA-A,B,DRB1 identical to patients waiting for unrelate d bone marrow transplantation. If a given patient presents unusual hap lotypes, the chance of finding HLA-B44 mismatches may be higher becaus e of the presence of different haplotype relationships in the donors.