Is there any impact of HLA-DPB1 disparity in 10/10 HLA-matched unrelated hematopoietic SCT? Results of a French multicentric retrospective study

Abstract

We retrospectively analyzed the impact of HLA-DPB1 mismatches in a large cohort of 1342 French patients who underwent 10/10 HLA-matched unrelated HSCT. A significant impact of HLA-DPB1 allelic mismatches (2 vs 0) was observed in severe acute GVHD (aGVHD III-IV) (risk ratio (RR) = 1.73, confidence interval (CI) 95% 1.09-2.73, P = 0.019) without impact on OS, TRM, relapse and chronic GVHD (cGVHD). According to the T-cell epitope 3 (TCE3)/TCE4 HLA-DPB1 disparity algorithm, 37.6% and 58.4% pairs had nonpermissive HLA-DPB1, respectively. TCE3 and TCE4 disparities had no statistical impact on OS, TRM, relapse, aGVHD and cGVHD. When TCE3/TCE4 disparities were analyzed in the graft-vs-host or host-vs-graft (HVG) direction, only a significant impact of TCE4 nonpermissive disparities in the HVG direction was observed on relapse (RR = 1.34, CI 95% 1.00-1.80, P = 0.048). In conclusion, this French retrospective study shows an adverse prognosis of HLA-DPB1 mismatches (2 vs 0) on severe aGVHD and of nonpermissive TCE4 HVG disparities on relapse after HLA-matched 10/10 unrelated HSCT.

Functional distance between recipient and donor HLA-DPB1 determines nonpermissive mismatches in unrelated HCT

“…For nonpermissive HLA-DPB1 TCE mismatches, the multivariate hazards of OS (HR, 1.15; 95% CI, 0.86-1.54; P , .360) were similar to those reported previously 4,9 (Table 2), but this was not significant in the present cohort. This finding is consistent with some previous reports, 31,55 suggesting that statistical power is an important parameter . The FD Allele score for individual HLA-DPB1 alleles, calculated as the sum of FD AA scores as shown in the figure, correlate well with TCE groups based on T-cell cross-reactivity patterns, and allow us to predict TCE group assignment for all known HLA-DPB1 alleles.…”

“…26, 27 These models did not prove equally valid for HCT outcome prediction, 23,28 probably reflecting the more complex nature of HLA-peptide recognition by the T-cell receptor (TCR) compared with allo-antibodies. 29,30 Here, we have addressed the functional role of AA polymorphism in HLA class II for clinical outcome of HCT in the context of nonpermissive TCE mismatches at HLA-DPB1, shown by some 4,9 but not all 31 multicenter studies to be associated with mortality after 10/10 HLA-matched unrelated HCT. We previously experimentally established a detailed landscape of the functional impact of single AA substitutions in HLA-DPB1 on in vitro T-cell allo-reactivity.…”

Clinical outcomes of HLA‐DPB1 mismatches in 10/10 HLA‐matched unrelated donor‐recipient pairs undergoing allogeneic stem cell transplant

“…Recent literature has suggested that matching at the HLA‐DPB1 locus, in addition to the standard loci, may impact outcomes in ASCT . The β‐chain of the HLA‐DP antigen is known to be highly polymorphic, with 716 alleles encoding 591 proteins and 19 null variants, while the α‐chain has 44 alleles encoding 22 proteins .…”

Impact of HLA-DPB1 Matching in Unrelated Allogeneic Stem Cell Transplantation: Results of Two Centers From Turkey

“…25 Another study from France, published by Gagne et al could only show an adverse prognosis in two HLA-DPB1 mismatches for severe aGVHD. 26 HLA-DPB1 disparities did not cause a worse outcome in terms of relapse and overall survival in this study. Similarly, the results of Pan et al showed that the presence of anti-HLA antibodies and their dynamic changes after transplantation were associated with increased occurrence of grades II to IV acute and chronic GVHD, higher treatment-related mortality, and reduced OS and disease-free survival.…”

“…[10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] For instance, in the study by Loiseau et al reported increased frequency of severe aGVHD and poorer survival in two HLA-DP incompatibilities in a group of unrelated ASCT patients. 10 In this study they were not able show a significant relationship between HLA-DP mismatches and disease relapse.…”