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 Dec;50(6):602-9. doi: 10.1111/j.1399-0039.1997.tb02918.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Marrow Transplantation / immunology*
  • Child
  • Gene Frequency
  • HLA-A Antigens / genetics
  • HLA-B Antigens / classification
  • HLA-B Antigens / genetics*
  • HLA-B44 Antigen
  • HLA-DR Antigens / genetics
  • Haplotypes
  • Histocompatibility Testing
  • Humans
  • Italy
  • Linkage Disequilibrium

Substances

  • HLA-A Antigens
  • HLA-B Antigens
  • HLA-B44 Antigen
  • HLA-DR Antigens