Mismatched HLA-DRB3 Can Induce a Potent Immune Response After HLA 10/10 Matched Stem Cell Transplantation. Issue 12 (December 2017)

• Record Type: Journal Article
• Authors: van Balen, Peter; van Luxemburg-Heijs, Simone A.P.; van de Meent, Marian; van Bergen, Cornelis A.M.; Halkes, Constantijn J.M.; Jedema, Inge; Falkenburg, J.H. Frederik
• Is Part Of: Transplantation. Volume 101:Issue 12(2017)
• Publication Date: 2017-12
• Subjects: Transplantation of organs, tissues, etc -- Periodicals; Transplantation immunology -- Periodicals; 617.95
• DOI: 10.1097/TP.0000000000001713
• Languages: English
• ISSNs: 0041-1337

Abstract

Abstract : 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. Abstract : Contrary to current assumptions, the authors demonstrate that in HLA-A, B, C and DRB1 full-matched recipients of allogeneic stem cell transplantation, mismatches at the DRB3, 4, 5 and DP may be responsible for polyclonal alloimmune response associated with conversion of chimerism and severe GVHD.