Integrating biological HLA-DPB1 mismatch models to predict survival after unrelated hematopoietic cell transplantation

Abstract

Not available.

Fine-tuning alloreactivity against HLA-DP to control leukemia with tolerable graft-<i>versus</i>-host disease

“…Overall survival is also improved for transplants from TCE-permissive donors over those from non-TCE permissive mismatched but not over HLA-DPB1 matched donors. 1 The development of large worldwide registries of HLA typed volunteers has allowed transplantation of compatible unrelated donor cells for most patients in need. However, because of the poor linkage disequilibrium between HLA-DP and the rest of the HLA haplotype, most donors have not been selected based on HLA-DPB1, so that about 80% of unrelated transplants have been mismatched at HLA-DPB1.…”

“…Overall survival is also improved for transplants from TCE-permissive donors over those from non-TCE permissive mismatched but not over HLA-DPB1 matched donors. 1 …”

“… 2-5 Their paper reports a significant interaction between high HLA-DPB1 expression in the host and donor HLA-DPB1 TCE-permissiveness in opposing directions, with lower mortality associated with donor TCE-permissiveness in the high-expression recipient group despite increased GvHD and decreased leukemia relapse. 1 …”

“…Mechanistically, there are strong data relating the HLA-DPB1 regulatory region variant rs9277534 with HLA-DPB1 expression, 2 increased GvHD, 2-3 and protection from relapse after allogeneic stem cell transplantation. 1 , 2 Furthermore, HLA class II downregulation has been associated with escape from immune control of leukemia after allogeneic stem cell transplantation. 6 Additional studies, however, should formally demonstrate that the HLA-DPB1 regulatory region variant rs9277534 is associated with HLA-DPB1 expression in leukemia, and that lower levels of HLA-DPB1 in leukemia increase the risk of relapse after allogeneic stem cell transplantation.…”

“… 4-5 Thus, it is not surprising that TCE-defined permissive HLA-DPB1 disparate donors protect recipients with high HLA-DPB1 expression from excess GvHD and mortality. 1 The mechanisms by which TCE-permissive HLA-DPB1 mismatches protect from excess alloreactivity and GvHD-dependent mortality have been related to a narrower functional distance compared to that of the non-permissive disparities, and selection of a narrower immunopeptidome. 7- 9 …”