title: Pathophysiology of ANCA-associated small vessel vasculitis.
abstract: Antineutrophil cytoplasmic autoantibodies (ANCAs) directed to proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA) are strongly associated with the ANCA-associated vasculitides--Wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome. Clinical observations, including the efficacy of B-cell depletion via rituximab treatment, support--but do not prove--a pathogenic role for ANCA in the ANCA-associated vasculitides. In vitro experimental studies show that the interplay of ANCA, neutrophils, the alternative pathway of the complement system, and endothelial cells could result in lysis of the endothelium. A pathogenic role for MPO-ANCA is strongly supported by in vivo experimental studies in mice and rats, which also elucidate the pathogenic mechanisms involved in lesion development. Unfortunately, an animal model for PR3-ANCA-associated Wegener's granulomatosis is not yet available. Here, cellular immunity appears to play a major role as well, particularly via interleukin-17-producing T cells, in line with granulomatous inflammation in the lesions. Finally, microbial factors, in particular Staphylococcus aureus and gram-negative bacteria, seem to be involved in disease induction and expression, but further studies are needed to define their precise role in disease development.
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, AA21, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands. c.g.m.kallenberg@reuma.umcg.nl
authors.forename: Cees G M
authors.initials: CG
authors.lastname: Kallenberg
mesh_terms: D000818:Animals; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D051379:Mice; D055953:Microscopic Polyangiitis / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D053146:Myeloblastin / Q000276:immunology; D009504:Neutrophils / Q000166:cytology / Q000276:immunology; D009195:Peroxidase / Q000276:immunology; D051381:Rats; D013211:Staphylococcus aureus / Q000276:immunology / Q000472:pathogenicity; D058504:Th17 Cells / Q000276:immunology
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D009195:Peroxidase; D053146:Myeloblastin