Mismatched HLA-DRB3 can induce a potent immune response after HLA 10/10 matched stem cell transplantation
P van Balen, SAP van Luxemburg-Heijs… - …, 2017 - journals.lww.com
P van Balen, SAP van Luxemburg-Heijs, M van de Meent, CAM van Bergen, CJM Halkes…
Transplantation, 2017•journals.lww.comBackground Donors for allogeneic stem cell transplantation are preferentially matched with
patients for HLA-A,-B,-C, and-DRB1. Mismatches between donor and patient in these alleles
are associated with an increased risk of graft-versus-host disease (GVHD). In contrast, HLA-
DRB3, 4 and 5, HLA-DQ and HLA-DP are usually assumed to be low expression loci with
limited relevance, although mismatches in HLA-DQ and HLA-DP can result in alloimmune
responses. Mismatches in HLA-DRB3, 4, and 5 are usually not taken into account in donor …
patients for HLA-A,-B,-C, and-DRB1. Mismatches between donor and patient in these alleles
are associated with an increased risk of graft-versus-host disease (GVHD). In contrast, HLA-
DRB3, 4 and 5, HLA-DQ and HLA-DP are usually assumed to be low expression loci with
limited relevance, although mismatches in HLA-DQ and HLA-DP can result in alloimmune
responses. Mismatches in HLA-DRB3, 4, and 5 are usually not taken into account in donor …
Background
Donors for allogeneic stem cell transplantation are preferentially matched with patients for HLA-A,-B,-C, and-DRB1. Mismatches between donor and patient in these alleles are associated with an increased risk of graft-versus-host disease (GVHD). In contrast, HLA-DRB3, 4 and 5, HLA-DQ and HLA-DP are usually assumed to be low expression loci with limited relevance, although mismatches in HLA-DQ and HLA-DP can result in alloimmune responses. Mismatches in HLA-DRB3, 4, and 5 are usually not taken into account in donor selection.
Methods
Conversion of chimerism in the presence of GVHD after CD4 donor lymphocyte infusion was observed in a patient, HLA 10/10 matched, but mismatched for HLA-DRB3 and HLA-DPB1 compared with the donor. Alloreactive CD4 T cells were isolated from peripheral blood after CD4 donor lymphocyte infusion and recognition of donor-derived target cells transduced with the mismatched patient variant HLA-DRB3 and HLA-DPB1 molecule was tested.
Results
A dominant polyclonal CD4 T cell response against patient's mismatched HLA-DRB3 molecule was found in addition to an immune response against patient’s mismatched HLA-DPB1 molecule. CD4 T cells specific for these HLA class II molecules recognized both hematopoietic target cells as well as GVHD target cells.
Conclusions
In contrast to the assumption that mismatches in HLA-DRB3, 4, and 5 are not of immunogenic significance after HLA 10/10 matched allogeneic stem cell transplantation, we show that in this matched setting not only mismatches in HLA-DPB1, but also mismatches in HLA-DRB3 may induce a polyclonal allo-immune response associated with conversion of chimerism and severe GVHD.
Lippincott Williams & Wilkins