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*02:01/DPB1*03:01 allelic mismatches were associated with decreased 2‐year OS and increased NRM. DPB1*02:02/DPB1*05:01 and DPB1*02:01/DPB1*05:01 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*02:02 ~ DPB1*05:01/DPA1*02:01 ~ DPB1*17:01 linkage mismatches were associated with lower 2‐year OS, especially among AML/MDS recipients. DPA1*02:02 ~ DPB1*05:01/DPA1*01:03 ~ DPB1*02:01 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.