Impact of HLA‐DPB1 allelic and single amino acid mismatches on HSCT

Abstract

SummaryThe interpretation of the role of HLA-DPB1 in unrelated haematopoietic stem cell transplantation (HSCT) is subject to discussion. We have investigated the role of HLA-DPB1 allele matching in HSCT outcomes in 161 recipients who were HLA-A, -B, -C, -DRB1 and -DQB1-matched with their unrelated donors at the allelic level (10/10). In addition, we analysed the association of polymorphic amino acid mismatches of DPB1 molecule with HSCT end-points, and a previously published permissiveness concept. HLA-DPB1 allele mismatches were significantly associated with an increased incidence of acute graft-versus-host disease (aGvHD) and worse overall survival (OS). The mismatch at amino acid position 69 significantly increased the risk for transplant-related mortality (TRM). Risk factors for aGvHD also included mismatches at positions 8, 9, 35, 76 and 84. This is to our knowledge, the first report of an in vivo effect of single amino acid mismatches on HSCT outcomes. In this study, grouping of allelic mismatches into permissive and non-permissive categories and their association with transplantation end-points was relevant for TRM but not for other clinical end-points.

How to select the best available related or unrelated donor of hematopoietic stem cells?

“…Evidence for a role of HLA-DPB1 mismatches is now well documented. 6,13,[23][24][25] In 10/10-matched HSCT, DRB3 and DRB4 mismatches were associated with poorer outcome, although most donor-recipient pairs were also incompatible for the DPB1 locus. 16 7/8-matched HSCT more than two mismatches at the DP, DQ and DRB3/4/5 loci were associated with an increased risk of mortality.…”

Tick-Borne Encephalitis (TBE) and Hepatitis B Nonresponders Feature Different Immunologic Mechanisms in Response to TBE and Influenza Vaccination with Involvement of Regulatory T and B Cells and IL-10

“…In the blood samples obtained for tissue typing, DNA was isolated either by salting-out method or GenoMTM-6 (GenoVision; VertriebsGesmbH, Vienna, Austria). HLA class II genes were typed at the high-resolution level by sequence-based typing and comprised HLA DRB1, DRB3/4/5, and DQB1 allele (21).…”

Nonpermissive HLA-DPB1 disparity is a significant independent risk factor for mortality after unrelated hematopoietic stem cell transplantation

“…Based on cross-reactive T-cell alloreactivity patterns, our group has previously described an algorithm for nonpermissive HLA-DPB1 mismatches, which were shown by us and subsequently by others to be significantly associated with transplant-related mortality but not with overall mortality (OM). [9][10][11] In the present study, we have modified this algorithm by integrating our functional data with those reported by others [12][13][14] and tested its clinical predictive value by retrospective analysis of 621 unrelated HSCT facilitated through the Italian Bone Marrow Donor Registry. The results provide compelling evidence that the clinical outcome of unrelated HSCT can be significantly improved by consideration of nonpermissive HLA-DPB1 disparity in donor selection.…”