HLA-DPB1 and DPA1 ~ DPB1 linkage mismatch affects the survival of recipients receiving HLA-14/14 matched unrelated donor HSCT.

ABSTRACT

To analyse the effect of HLA-DPA1 and HLA-DPB1 allelic mismatches on the outcomes of unrelated donor haematopoietic stem cell transplantation (URD-HSCT), we collected 258 recipients with haematological disease who underwent HLA-10/10 matched URD-HSCT. HLA-A, -B, -C, -DRB1, -DQB1, -DRB3/4/5, -DQA1, -DPA1 and -DPB1 typing was performed for the donors and recipients using next-generation sequencing (NGS) technology. After excluding 8 cases with DQA1 or DRB3/4/5 mismatches, we included 250 cases with HLA-14/14 matching for further analysis. Our results showed that the proportion of matched DPA1 and DPB1 alleles was only 10.4% (26/250). The remaining 89.6% of donors and recipients demonstrated DPA1 or DPB1 mismatch. In the DPA1 matched and DPB1 mismatched group, accounting for 18.8% (47/250) of the cohort, DPB1*0201/DPB1*0301 allelic mismatches were associated with decreased 2-year OS and increased NRM. DPB1*0202/DPB1*0501 and DPB1*0201/DPB1*0501 mismatches showed no impact on outcomes. Moreover, the specific allelic mismatches observed were consistent with the DPB1 T-cell epitope (TCE) classification as permissive and non-permissive. We innovatively established an analysis method for DPA1 ~ DPB1 linkage mismatch for cases with both DPA1 and DPB1 mismatched, accounting for 70% (175/250) of the total. DPA1*0202 ~ DPB1*0501/DPA1*0201 ~ DPB1*1701 linkage mismatches were associated with lower 2-year OS, especially among AML/MDS recipients. DPA1*0202 ~ DPB1*0501/DPA1*0103 ~ DPB1*0201 linkage mismatches showed no impact on outcomes. In conclusion, applying the DPA1 ~ DPB1 linkage mismatch analysis approach can identify different types of mismatches affecting transplant outcomes and provide valuable insight for selecting optimal donors for AML/MDS and ALL recipients.