A deduced probable HLA-DRB1*16:35-associated HLA haplotype (A*11-B*13-DRB1*16:35) found in a case analysis of two Taiwanese unrelated bone marrow hematopoietic stem cell donors

OBJECTIVE: HLA-DRB1*16:35 is a low incidence allele in the HLA-DRB1 locus. The objective of this study is to report the ethnicity of DRB1*16:35 and its deduced probable HLA associated haplotype in two Taiwanese unrelated bone marrow hematopoietic stem cell donors and to determine its variation from DRB1*16:02:01 and DRB1*16:01:01. MATERIALS AND METHODS: A sequence-based typing method was employed to confirm the low incidence allele DRB1*16:35. Polymerase chain reaction was performed to amplify exon 2 and exon 3 of the HLA-A and HLA-B loci and exon 2 of the HLA-DRB1 locus using group-specific primer sets. The amplicons were sequenced employing BigDye Terminator Cycle Sequencing Ready Reaction kits in both directions according to the manufacturer's protocols. RESULTS: The DNA sequence of DRB1*16:35 is identical to DRB1*16:02:01 in exons 2, except for residue 364 where the C of DRB1*16:02:01 is replaced by the T of DRB1*16:35 (codon 93, CGG->TGG). The nucleotide exchange leads to an amino acid alteration to the protein sequence of DRB1*16:02:01 at residue 93 where the arginine (R) of DRB1*16:02:01 is changed to the tryptophan (W) of DRB1*16:35. We deduced the probable HLA haplotype in association with DRB1*16:35 in Taiwanese to be A*11-B*13- DRB1*16:35. CONCLUSION: Information on the deduced probable HLA haplotype in association with the low incidence DRB1*16:35 allele that we report here is of value for HLA testing laboratories for reference purposes. In addition, it can be used by stem cell transplantation donor search coordinators to determine a strategy for finding compatible donors in unrelated bone marrow donor registries when a patient has this uncommon HLA allele.