title: Donor Specific Antibodies are not only directed against HLA-DR: Minding your Ps and Qs.
abstract: During solid organ transplantation, interactions between recipient and donor immune cells occur chiefly in the allograft microvasculature. All three HLA class II antigens, DR, DP and DQ, have been detected on renal EC with a markedly increased expression of HLA class II observed in renal allografts undergoing rejection. Recent studies of donor-specific antibodies (DSA) have exposed the prevalence of de novo DSA directed against HLA-DQ, as well as a strong association between these antibodies and allograft damage. The HLA-DQ molecule can be distinguished from the other class II antigens by its transcription, expression and peptide repertoire. The distinct intragraft expression and immunogenicity of HLA-DQ may contribute to the incidence of HLA-DQ DSA, as well as directing the DSA-mediated damage. The possibility of HLA class II antigen-specific signaling in EC may reveal different mechanisms of allograft damage that act in tandem with complement-dependent injury. This review addresses the features of the HLA-DQ heterodimer that may underlie the high incidence of HLA-DQ directed DSA and their association with allograft damage. We also consider existing data in hematopoietic stem cell transplantation concerning HLA directed DSA.
authors.affiliation: INSERM UMRs 1160, Institut Universitaire d'Hématologie, Université Paris Diderot, Hôpital Saint Louis, Paris 75010, France; LabEx Transplantex, AP-HP, Hôpital Saint-Louis, Paris 75010, France.
authors.forename: Amy R
authors.initials: AR
authors.lastname: Cross
authors.affiliation: INSERM UMRs 1160, Institut Universitaire d'Hématologie, Université Paris Diderot, Hôpital Saint Louis, Paris 75010, France; LabEx Transplantex, AP-HP, Hôpital Saint-Louis, Paris 75010, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Lion
authors.affiliation: INSERM UMRs 1160, Institut Universitaire d'Hématologie, Université Paris Diderot, Hôpital Saint Louis, Paris 75010, France; LabEx Transplantex, AP-HP, Hôpital Saint-Louis, Paris 75010, France; Laboratoire de Histocompatibilité, Hôpital Saint Louis, Paris 75010, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Loiseau
authors.affiliation: Laboratoire de Histocompatibilité, Hôpital Saint Louis, Paris 75010, France; Université Paris Diderot, Sorbonne Paris Cité, F-75013, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Charron
authors.affiliation: INSERM UMRs 1160, Institut Universitaire d'Hématologie, Université Paris Diderot, Hôpital Saint Louis, Paris 75010, France; LabEx Transplantex, AP-HP, Hôpital Saint-Louis, Paris 75010, France; Laboratoire de Histocompatibilité, Hôpital Saint Louis, Paris 75010, France; Université Paris Diderot, Sorbonne Paris Cité, F-75013, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Taupin
authors.affiliation: INSERM UMRs 1160, Institut Universitaire d'Hématologie, Université Paris Diderot, Hôpital Saint Louis, Paris 75010, France; LabEx Transplantex, AP-HP, Hôpital Saint-Louis, Paris 75010, France; Service de Néphrologie et Transplantation, Hôpital Saint Louis, Paris 75010, France; Université Paris Diderot, Sorbonne Paris Cité, F-75013, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Glotz
authors.affiliation: INSERM UMRs 1160, Institut Universitaire d'Hématologie, Université Paris Diderot, Hôpital Saint Louis, Paris 75010, France; LabEx Transplantex, AP-HP, Hôpital Saint-Louis, Paris 75010, France. Electronic address: nuala.mooney@univ-paris-diderot.fr.
authors.forename: Nuala
authors.initials: N
authors.lastname: Mooney
mesh_terms: D000920:Antibody-Dependent Cell Cytotoxicity; D000939:Epitopes; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology; D006682:HLA-DP Antigens / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D056724:Immunity, Humoral; D007518:Isoantibodies / Q000378:metabolism; D016030:Kidney Transplantation; D014181:Transplantation Immunology
chemical_list: D000939:Epitopes; D006682:HLA-DP Antigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D007518:Isoantibodies
keywords: Antibody-mediated rejection; Donor-specific-antibodies; Endothelial cell; HLA-DP; HLA-DQ