title: Association of high HLA-E expression during acute cellular rejection and numbers of HLA class I leader peptide mismatches with reduced renal allograft survival.
abstract: Non-classical Human Leukocyte Antigen (HLA)-E preferentially presents leader peptides derived from classical HLA-class I molecules. HLA-E can trigger opposed immune responses by interacting with inhibitory NKG2A or by activating NKG2C receptors on NK and T-cells. We studied the impact of HLA-E on renal allograft survival during acute cellular rejection. HLA-E expression was up-regulated in acute cellular rejection (ACR) biopsies (n=12) compared to biopsies from 13 renal allografts with no rejection-signs. HLA-E up-regulation was correlated with numbers of HLA-class I leader peptide mismatches (p=0.04). CD8+ and CD56+ infiltrating cells correlated with HLA-E expression (p<0.0001 and p=0.0009, respectively). Activating NKG2C receptor dominated on effector cells in biopsies and peripheral blood during ACR potentially allowing HLA-E-mediated immune activation. Moreover, HLA-E expression correlated with deterioration in renal allograft function (p<0.008) and reduced allograft survival (p=0.002). Our findings provide evidence that during renal allograft rejection HLA-E along with high numbers of mismatched HLA-class I leader peptides might represent additional targets for immune-activating responses.
authors.affiliation: Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Essen, Germany; Department of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Essen, Germany. Electronic address: hana.guberina@uk-essen.de.
authors.forename: Hana
authors.initials: H
authors.lastname: Guberina
authors.affiliation: Institute for Transfusion Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Rebmann
authors.affiliation: Institute for Transfusion Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Wagner
authors.affiliation: Institute for Transfusion Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany; CAPES Foundation, Ministry of Education of Brazil, Brasília, DF 70.040-020, Brazil.
authors.forename: Fabiola
authors.initials: F
authors.lastname: da Silva Nardi
authors.affiliation: Institute for Transfusion Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Phillip
authors.initials: P
authors.lastname: Dziallas
authors.affiliation: Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Essen, Germany; Department of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Dolff
authors.affiliation: Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Bienholz
authors.affiliation: Institute for Pathology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Jeremias
authors.initials: J
authors.lastname: Wohlschlaeger
authors.affiliation: Institute for Pathology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Agnes
authors.initials: A
authors.lastname: Bankfalvi
authors.affiliation: Institute for Transfusion Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Falko M
authors.initials: FM
authors.lastname: Heinemann
authors.affiliation: Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Essen, Germany; Department of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Witzke
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden, The Netherlands, Netherlands.
authors.forename: Yvonne M
authors.initials: YM
authors.lastname: Zoet
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden, The Netherlands, Netherlands.
authors.forename: Frans H J
authors.initials: FH
authors.lastname: Claas
authors.affiliation: Institute for Transfusion Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Horn
authors.affiliation: Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kribben
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden, The Netherlands, Netherlands.
authors.forename: Ilias I N
authors.initials: II
authors.lastname: Doxiadis
mesh_terms: D015415:Biomarkers; D001706:Biopsy; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology*; D006085:Graft Survival / Q000235:genetics / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D055650:NK Cell Lectin-Like Receptor Subfamily A / Q000378:metabolism; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014184:Transplantation, Homologous; D000097625:HLA-E Antigens
chemical_list: D015415:Biomarkers; D015395:Histocompatibility Antigens Class I; D055650:NK Cell Lectin-Like Receptor Subfamily A; D055654:NK Cell Lectin-Like Receptor Subfamily C; D000097625:HLA-E Antigens
keywords: Acute cellular rejection; Adaptive immunity; HLA class I leader peptides; HLA-E; NKG2C; Renal transplantation