title: Identification of target antigens of anti-endothelial cell antibodies in patients with anti-neutrophil cytoplasmic antibody-associated vasculitides: a proteomic approach.
abstract: Anti-endothelial cell antibodies (AECAs) have been reported to cause endothelial cell dysfunction, but their specific targets have never been identified in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs). Proteins from human umbilical vein endothelial cells (HUVECs) were separated by 2-dimensional electrophoresis (2-DE). 2-D immunoblots were used to compare serum IgG reactivities from 30 patients with AAV and 12 healthy controls (HCs). Proteins identified as target antigens by MALDI- TOF-TOF mass spectrometry included lamin A/C, vimentin, α-enolase, far upstream binding protein 2 (FUBP2) and protein disulfide-isomerase A3 precursor (PDIA3). Antibodies targeting lamin A, vimentin, α-enolase, FUBP2 and PDIA3 were identified in 57.1%, 64.3%, 35.7%, 50% and 0% of patients with microscopic polyangiitis and 8%, 3.3%, 7.2%, 0% and 6.7% of HCs respectively. IgG from patients with microscopic polyangiitis had stronger reactivity against HUVEC than other groups and HCs and induced stronger Erk phosphorylation in HUVECs than IgG from HCs.
authors.affiliation: Institut Cochin, INSERM U1016, CNRS UMR 8104, Université Paris Descartes, 22 rue Méchain, 75014 Paris, France; Pôle de Médecine Interne, Centre de Référence pour les vascularites nécrosantes et la sclérodermie systémique, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, 27 rue du Faubourg Saint-Jacques, F-75679 Paris Cedex 14, France. Electronic address: alexisregent@hotmail.com.
authors.forename: Alexis
authors.initials: A
authors.lastname: Régent
authors.affiliation: Institut Cochin, INSERM U1016, CNRS UMR 8104, Université Paris Descartes, 22 rue Méchain, 75014 Paris, France. Electronic address: sebastien.lofek@gmail.com.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lofek
authors.affiliation: Institut Cochin, INSERM U1016, CNRS UMR 8104, Université Paris Descartes, 22 rue Méchain, 75014 Paris, France. Electronic address: hanadi_dib@hotmail.fr.
authors.forename: Hanadi
authors.initials: H
authors.lastname: Dib
authors.affiliation: Pôle de Médecine Interne, Centre de Référence pour les vascularites nécrosantes et la sclérodermie systémique, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, 27 rue du Faubourg Saint-Jacques, F-75679 Paris Cedex 14, France. Electronic address: guillaume.bussone@cch.aphp.fr.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bussone
authors.affiliation: Institut Cochin, INSERM U1016, CNRS UMR 8104, Université Paris Descartes, 22 rue Méchain, 75014 Paris, France. Electronic address: nicolas.tamas@parisdescartes.fr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tamas
authors.affiliation: Institut Cochin, INSERM U1016, CNRS UMR 8104, Université Paris Descartes, 22 rue Méchain, 75014 Paris, France; Plate-forme Protéomique 3P5, Université Paris Descartes, Sorbonne Paris Cité, 22 rue Méchain, 75014 Paris, France. Electronic address: christian.federici@inserm.fr.
authors.forename: Christian
authors.initials: C
authors.lastname: Federici
authors.affiliation: Institut Cochin, INSERM U1016, CNRS UMR 8104, Université Paris Descartes, 22 rue Méchain, 75014 Paris, France; Plate-forme Protéomique 3P5, Université Paris Descartes, Sorbonne Paris Cité, 22 rue Méchain, 75014 Paris, France. Electronic address: cedric.broussard@inserm.fr.
authors.forename: Cédric
authors.initials: C
authors.lastname: Broussard
authors.affiliation: Institut Cochin, INSERM U1016, CNRS UMR 8104, Université Paris Descartes, 22 rue Méchain, 75014 Paris, France; Pôle de Médecine Interne, Centre de Référence pour les vascularites nécrosantes et la sclérodermie systémique, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, 27 rue du Faubourg Saint-Jacques, F-75679 Paris Cedex 14, France. Electronic address: loic.guillevin@cch.aphp.fr.
authors.forename: Loïc
authors.initials: L
authors.lastname: Guillevin
authors.affiliation: Institut Cochin, INSERM U1016, CNRS UMR 8104, Université Paris Descartes, 22 rue Méchain, 75014 Paris, France; Pôle de Médecine Interne, Centre de Référence pour les vascularites nécrosantes et la sclérodermie systémique, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, 27 rue du Faubourg Saint-Jacques, F-75679 Paris Cedex 14, France. Electronic address: luc.mouthon@cch.aphp.fr.
authors.forename: Luc
authors.initials: L
authors.lastname: Mouthon
mesh_terms: D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D001324:Autoantigens / Q000097:blood / Q000276:immunology*; D001327:Autoimmune Diseases / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism; D042783:Endothelial Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D061307:Human Umbilical Vein Endothelial Cells / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D060066:Protein Interaction Maps; D040901:Proteomics / Q000379:methods; D015398:Signal Transduction; D014657:Vasculitis / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D001324:Autoantigens; D007074:Immunoglobulin G; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: Anti-neutrophil cytoplasmic antibodies; Autoantibodies; Erk; Human umbilical vein endothelial cell; Lamin; Vasculitides