title: New pathophysiological insights and treatment of ANCA-associated vasculitis.
abstract: ANCA-associated-vasculitis (AAV) comprises three different diseases entities: Churg-Strauss syndrome, microscopic polyangiitis, and Wegener's granulomatosis. AAV is an autoimmune disease with complex pathophysiology. Anti-neutrophil cytoplasmic antibodies (ANCAs) with specificity for proteinase-3 (PR3) or myeloperoxidase (MPO) are hallmarks of AAV and have a pivotal role in disease development. In addition to ANCA, the cellular immune system contributes to the pathogenesis of the disease. ANCA-mediated degranulation of neutrophils causes vasculitic damage; T cells drive granuloma formation, promote vasculitic damage by several different pathways, and enhance autoantibody production by B cells. Recently, complementary PR3 and lysosomal membrane protein-2 were suggested as novel autoantigens in AAV. New findings also indicate the importance of complement, danger-associated molecular patterns, and dendritic cells in AAV. This review highlights novel pathophysiological findings in AAV and puts them into context with the current understanding of disease mechanisms. Furthermore, implications for present and new therapeutic strategies are discussed.
authors.affiliation: Department of Internal Medicine, Division of Clinical and Experimental Immunology, University Hospital Maastricht, Maastricht, The Netherlands; Department of Nephrology, University Duisburg-Essen, Essen, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wilde
authors.affiliation: Department of Internal Medicine, Division of Clinical and Experimental Immunology, University Hospital Maastricht, Maastricht, The Netherlands.
authors.forename: Pieter
authors.initials: P
authors.lastname: van Paassen
authors.affiliation: Department of Nephrology, University Duisburg-Essen, Essen, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Witzke
authors.affiliation: Department of Internal Medicine, Division of Clinical and Experimental Immunology, University Hospital Maastricht, Maastricht, The Netherlands. Electronic address: Secretariaat-IMMUNO@IMMUNO.unimaas.nl.
authors.forename: Jan Willem Cohen
authors.initials: JWC
authors.lastname: Tervaert
mesh_terms: D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy*; D015551:Autoimmunity; D003165:Complement System Proteins / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008221:Lymphoid Tissue / Q000276:immunology; D017410:Practice Guidelines as Topic; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D003165:Complement System Proteins