title: Anti-endothelial cell IgG antibodies from patients with Wegener's granulomatosis bind to human endothelial cells in vitro and induce adhesion molecule expression and cytokine secretion.
abstract: OBJECTIVE
  To elucidate the role of anti-endothelial cell antibodies (AECA) in vascular inflammation in patients with Wegener's granulomatosis (WG).
  
  
  METHODS
  IgG fractions from 3 AECA-positive WG patients, IgG from 3 AECA-negative WG patients, and IgG from healthy donors were tested for their ability to: a) bind to endothelial cells and to display complement-dependent or antibody-dependent cellular cytotoxicity, b) modulate cell membrane expression of adhesion molecules, as evaluated by cytofluorometry and by immunoenzymatic assay, and c) induce the secretion of interleukin-1 beta (IL-1 beta), IL-6, IL-8, and monocyte chemotactic protein 1 (MCP-1).
  
  
  RESULTS
  We found that AECA IgG from WG patients do not display any significant cytotoxicity but are able to up-regulate the expression of E-selectin, intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 and to induce the secretion of IL-1 beta, IL-6, IL-8, and MCP-1.
  
  
  CONCLUSIONS
  AECA in patients with WG could play a potential pathogenetic role by activating endothelial cells, and thus facilitating leukocyte recruitment and adhesion to endothelial surfaces, rather than by displaying a cytotoxic activity.
authors.affiliation: Instituto di Medicina Interna, University of Milan, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Del Papa
authors.forename: L
authors.initials: L
authors.lastname: Guidali
authors.forename: M
authors.initials: M
authors.lastname: Sironi
authors.forename: Y
authors.initials: Y
authors.lastname: Shoenfeld
authors.forename: A
authors.initials: A
authors.lastname: Mantovani
authors.forename: A
authors.initials: A
authors.lastname: Tincani
authors.forename: G
authors.initials: G
authors.lastname: Balestrieri
authors.forename: A
authors.initials: A
authors.lastname: Radice
authors.forename: R A
authors.initials: RA
authors.lastname: Sinico
authors.forename: P L
authors.initials: PL
authors.lastname: Meroni
mesh_terms: D001323:Autoantibodies / Q000032:analysis* / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic; D004730:Endothelium, Vascular / Q000737:chemistry / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D014890:Granulomatosis with Polyangiitis / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D014471:Umbilical Veins / Q000737:chemistry / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D015815:Cell Adhesion Molecules; D016207:Cytokines; D007074:Immunoglobulin G; C087589:anti-endothelial cell antibody