HLA‐B44 subtypes and the chance of finding HLA compatible donor/recipient pairs for bone marrow transplantation: a haplotype study of 303 Italian families

Abstract

A total of 1176 HLA‐A,B,DR haplotypes were reconstructed by typing 303 unrelated families referred to our laboratory during the last seven years for the search of HLA identical sibs in view of bone marrow transplantation. 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 knowledge of the HLA‐B44 haplotype relationships might prove useful for the programming of registries of unrelated bone marrow donors. Eighty five serologically defined HLA‐B44 unrelated subjects, either one or both parents from the above families, were subtyped by a high‐resolution sequence‐specific oligonucleotide probing approach. Moreover, 34 unrelated 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 alleles, appeared in strong, statistically significant, linkage disequilibrium with HLA‐A29, ‐A23 and ‐DR7. On the other hand, B*4402, which covered virtually all other B44 alleles, showed prevalent gametic associations with HLA‐A2 and HLA‐A24. The linkage disequilibrium between HLA alleles is the key for the low frequency of HLA‐B44 mismatches in donors selected as HLA‐A,B,DRB1 identical to patients waiting for unrelated bone marrow transplantation. If a given patient presents unusual haplotypes, the chance of finding HLA‐B44 mismatches may be higher because of the presence of different haplotype relationships in the donors. P. L. Mattiuz, E. Di Paolo, V Fossombroni, A. Menicucci, F. Pradella, B. Porfirio, G. Rombolá. HLA‐B44 subtypes and the chance of finding HLA compatible donor/recipient pairs for bone marrow transplantation: a haplotype study of 303 Italian families. Tissue Antigens 1997: 50: 602–609. Munksgaard, 1997 A total of 1176 HLA‐A,B,DR haplotypes were reconstructed by typing 303 unrelated families referred to our laboratory during the last seven years for the search of HLA identical sibs in view of bone marrow transplantation. 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 knowledge of the HLA‐B44 haplotype relationships might prove useful for the programming of registries of unrelated bone marrow donors. Eighty five serologically defined HLA‐B44 unrelated subjects, either one or both parents from the above families, were subtyped by a high‐resolution sequence‐specific oligonucleotide probing approach. Moreover, 34 unrelated 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 alleles, appeared in strong, statistically significant, linkage disequilibrium with HLA‐A29, ‐A23 and ‐DR7. On the other hand, B*4402, which covered virtually all other B44 alleles, showed prevalent gametic associations with HLA‐A2 and HLA‐A24. The linkage disequilibrium between HLA alleles is the key for the low frequency of HLA‐B44 mismatches in donors selected as HLA‐A,B,DRB1 identical to patients waiting for unrelated bone marrow transplantation. If a given patient presents unusual haplotypes, the chance of finding HLA‐B44 mismatches may be higher because of the presence of different haplotype relationships in the donors.