Mismatched HLA-DRB3 Can Induce a Potent Immune Response After HLA 10/10 Matched Stem Cell Transplantation
Autor: | Inge Jedema, Constantijn J.M. Halkes, Peter van Balen, Marian van de Meent, J.H. Frederik Falkenburg, Cornelis A.M. van Bergen, Simone A.P. van Luxemburg-Heijs |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
CD4-Positive T-Lymphocytes
Male HLA-DP Antigens T-Lymphocytes Graft vs Host Disease Human leukocyte antigen Biology Chimerism Donor lymphocyte infusion 03 medical and health sciences 0302 clinical medicine Immune system HLA Antigens HLA-DQ Antigens Humans Transplantation Homologous Alleles HLA-DRB3 Transplantation Donor selection Remission Induction Middle Aged Precursor Cell Lymphoblastic Leukemia-Lymphoma Tissue Donors Haematopoiesis Treatment Outcome 030220 oncology & carcinogenesis Blood Group Incompatibility Immunology Stem cell HLA-DRB3 Chains 030215 immunology Stem Cell Transplantation |
Zdroj: | Transplantation, 101(12), 2850-2854 |
Popis: | 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. |
Databáze: | OpenAIRE |
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