Human leucocyte antigen (HLA) DPB1 mismatched donors are often used for haematopoietic cell transplantation (HCT) due to the lack of fully matched donors. In order to reduce the risk of acute graft versus host disease (GVHD) due to HLA-DPB1 mismatching, donors with a permissive T cell epitope mismatch or a lower level of HLA-DPB1 antigen expression are preferred. HLA-DPB1 expression has been associated with the rs9277534A/G SNP in the 3’UTR of HLA-DPB1 and also with the exon 3 sequence of HLA-DPB1. This study examines HLA-DPB1 genotypes related to protein expression in the New Zealand population.
The study includes 10,633 patients and donors HLA-DPB1 typed by next generation sequencing from 2017-2023, as part of routine HLA typing for solid organ or haematopoietic cell transplantation. HLA-DPB1 alleles were assigned using Illumina Assign TruSight HLA v2.1 or GenDx NGSengine software. The rs9277534A/G SNP in the 3’UTR of HLA-DPB1 was defined using Illumina Assign TruSight HLA v2.1 for the unique HLA-DPB1 alleles. The HLA-DPB1 exon 3 sequence and 3’UTR rs9277534A/G SNP correlation was assessed.
There were 103 unique HLA-DPB1 alleles identified in this cohort, the 3’UTR rs9277534A/G SNP was defined for 85 HLA-DPB1 alleles. All but three alleles showed the expected correlation between the 3’UTR rs9277534A/G SNP and the HLA-DPB1 exon 3 sequence. HLA-DPB1*02:01:25 had the low expression rs9277534A SNP, but showed a single base difference at codon position 118.3 compared to that expected for a low expression allele. HLA-DPB1*03:01:08 and HLA-DPB1*296:01 both had the high expression rs9277534G SNP, but had a single base difference at codon position 167.3, compared to the expected exon 3 sequence.
This study suggests codon positions 118.3 and 167.3 of exon 3 may not be as strongly linked to the 3’UTR rs9277534A/G SNP as the other polymorphic regions of exon 3, and the 3’UTR rs9277534A/G SNP may be needed to check the expression level of HLA-DPB1 alleles for HCT patients and donors.