Recognition of the three deduced probable HLA haplotypes that are associated with HLA-C∗16:04:01 (A∗33:03-B∗44:02-C∗16:04:01-DRB1∗11:04:01 and A∗24-B∗44:02-C∗16:04:01-DRB1∗11:04) and HLA-B∗15:109 (A∗11-B∗15:109-DRB1∗04) in Taiwanese unrelated hematopoieti

Kuo-Liang Yang^{a, b}, Reuy-Ho Kao^a, Chin-Lon Lina, Py-Yu Lin^a

^a Laboratory of Immunogenetics, Tzu Chi Cord Blood Bank and Buddhist Tzu Chi Marrow Donor Registry, Buddhist Tzu Chi Stem Cells Centre, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
^b Department of Laboratory Medicine, Tzu Chi University, Hualien, Taiwan

Full-Text HTML |  Download PDF

Abstract
Objective

HLA-C∗16:04:01 and HLA-B∗15:109 are two uncommon alleles at the HLA-C locus and HLA-B locus, respectively. The objective of this study is to report the deduced probable human leukocyte antigen (HLA) haplotypes associated with HLA-C∗16:04:01 and HLA-B∗15:109 among Taiwanese unrelated bone marrow hematopoietic stem cell donors.

Materials and methods

A sequence-based typing method was employed to confirm the two low incidence alleles observed. Polymerase chain reaction was performed to amplify exons 2 and 3 of the HLA-A, and HLA-B loci with group-specific primer sets. Amplicons were sequenced using a BigDye Terminator Cycle Sequencing Ready Reaction Kit in both directions according to the manufacturer's protocols.

Results

The DNA sequence of C∗16:04:01 is identical to that of C∗16:01:01 in exons 2 and 3, except for two nucleotide substitutions at residues 538 (C->T) and 539 (A->G), which results in a single amino acid replacement at position 156 (glutamine->tryptophan). We deduced two probable HLA haplotypes that are found in association with C∗16:04:01 as A∗33:03-B∗44:02-C∗16:04:01-DRB1∗11:04 and A∗24-B∗44:02-C∗16:04:01-DRB1∗11:04. The DNA sequence of B∗15:109 is identical to B∗15:27:01 in exons 2 and 3 except for one nucleotide substitution at residue 200 (C->T), which results in a single amino acid replacement at position 43 (proline->leucine). A probable HLA haplotype associated with B∗15:109 was deduced to be A∗11-B∗15:109-DRB1∗04.

Conclusion

Information on the deduced HLA haplotypes that are found in association with the rare C∗16:04:01 and B∗15:109 alleles that we report here is useful for reference purposes at HLA testing laboratories and will help stem cell transplantation donor search coordinators when they are determining the likelihood of finding a compatible donor for patients bearing these two uncommon HLA alleles from unrelated bone marrow donor registries.

Keywords
Haplotypes; Hematopoietic stem cell; HLA; Sequence-based typing; Transplantation