Aim: While the role of HLA-DPB1 mismatches in allogeneic hematopoietic stem cell transplantation (aHSCT) has been extensively discussed, its interaction with acute graft-versus-host disease (aGvHD) remains unclear due to its permissiveness. Thus, this retrospective study aimed to investigate the association between permissive HLA-DPB1 mismatch and aGvHD after unrelated aHSCT for the treatment of hematologic malignancies.
Methods: Next generation sequencing was performed for high-resolution HLA typing of the DPB1 locus in samples from 74 donor–recipient pairs who initially underwent HLA 10/10 matched transplantation at our center between 2010 to 2023. aGvHD was classified according to the criteria of NIH as grades I, II, III, and IV. The classification of permissiveness HLA-DPB1 mismatches was based on three biological models (TCE, PIRCHE and Expression) and was determined using the IPD-IMGT/HLA and PIRCHE databases and the SNP rs9277534A/G, respectively. Statistical analysis was performed using RStudio v4.4.1.
Results: Ten (14%) recipients developed grade I aGvHD, 19 (26%) had grade II, four (5%) had grade III, and 41 (55%) did not develop aGvHD. No grade IV cases were observed. Among the 74 donor-recipient pairs, 20 (26,5%) were HLA 12/12 matched, 41 (55%) had one HLA-DPB1 mismatch and 14 (18,5%) had two HLA-DPB1 mismatches. However, among the 20 recipients with HLA 12/12 matched aHSCT, only four (20%) developed grade II-III aGvHD. Regarding the TCE model, 12 pairs had TCE-1 and 16 pairs had TCE-2 non-permissive mismatches while 11 pairs had TCE-3 core and 15 pairs TCE-3 noncore permissive mismatches. Analyses revealed a greater risk non-permissive TCE-1 mismatches for grade II-III aGvHD (OR=5.60; p=0.033). For the PIRCHE model, DPB1 mismatches had PIRCHE-I scores ranging from 0.00 to 9.00 and PIRCHE-II scores ranging from 0.00 to 19.00. Analyses indicate an increased risk when the PIRCHE-I score exceeded 5.00 and PIRCHE-II score exceeded 10.00 for grade II-III aGvHD (OR=4.80; p=0.057 and OR=5.60; p=0.033, respectively). The presence of non-permissive DPB1 combined with rs9277534GG alleles and a PIRCHE-II score above 10.00 suggested an increased risk of grade II-III aGvHD (OR=8.00; p=0.032).
Conclusion: This study suggests a possible association between non-permissive HLA-DPB1 alleles and PIRCHE-II with an increased risk of grade II-III aGvHD in unrelated aHSCT.
