title: Do antineutrophil cytoplasmic autoantibodies cause Wegener's granulomatosis and other forms of necrotizing vasculitis?
abstract: The in vitro experimental observations support the theoretical pathogenic scenario depicted in Figure 14. A similar scenario could be portrayed for monocytes. ANCA in the circulation are unable to interact with unprimed neutrophils because the target antigens are within the cytoplasm (Fig. 14A). Synergistic priming of neutrophils, e.g., by an infection, causes small amounts of target antigens to be released at the cell surface (Fig. 14B) where they can interact with ANCA (Fig. 14C). ANCA-activated neutrophils then adhere to endothelial cells via adhesion molecule interactions that may require prior priming of the endothelial cells (Fig. 14C). These activated and adherent neutrophils then injure endothelial cells (and eventually underlying vessel wall structures) by releasing granule enzymes and toxic oxygen metabolites (Fig. 14D). Although many research groups throughout the world have been attempting to create an animal model of ANCA-induced disease based on the theoretical paradigm proposed in Figure 14, as well as on other paradigms, no one has reported complete success. Until this is accomplished, the role of ANCA in the pathogenesis of Wegener's granulomatosis and other forms of ANCA-associated vasculitides will remain conjectural.
authors.affiliation: Department of Pathology, University of North Carolina, Chapel Hill.
authors.forename: J C
authors.initials: JC
authors.lastname: Jennette
authors.forename: B H
authors.initials: BH
authors.lastname: Ewert
authors.forename: R J
authors.initials: RJ
authors.lastname: Falk
mesh_terms: D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies / Q000276:immunology*; D001773:Blood Cells / Q000276:immunology; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D014890:Granulomatosis with Polyangiitis / Q000276:immunology*; D006801:Humans; D007962:Leukocytes / Q000276:immunology / Q000502:physiology; D009336:Necrosis; D014657:Vasculitis / Q000276:immunology*
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies