title: Complement system activation in ANCA vasculitis: A translational success story?
abstract: The ANCA-associated vasculitides (AAV) are characterized by pauci-immune necrotizing small to medium size vessel vasculitis frequently including necrotizing crescentric glomerulonephritis. Neutrophil activation by ANCA appears a primary pathogenic event. More recently, the complement system has been shown to be involved as well. Activation of the alternative pathway of complement, at least in part via activated neutrophils, results, amongst others, in the generation of C5a, a strong chemoattractant for neutrophils. C5a is also effective in neutrophil priming, a process leading to surface expression of the ANCA antigens so enabling neutrophils to be further activated by ANCA. Both in vitro and in vivo experimental data and histopathological studies from AAV patients underscore the role of complement, and particularly of C5a, in the pathophysiology of AAV. Preliminary data show that blocking of the C5a-receptor is a promising approach in the treatment of AAV.
authors.affiliation: Dept of Rheumatology & Clinical Immunology, University of Groningen, University Medical Center Groningen, The Netherlands. Electronic address: c.g.m.kallenberg@umcg.nl.
authors.forename: Cees G M
authors.initials: CG
authors.lastname: Kallenberg
authors.affiliation: Dept of Pathology & Medical Biology, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Heeringa
mesh_terms: D000818:Animals; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000235:genetics*; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D002986:Clinical Trials as Topic; D015936:Complement C5a / Q000235:genetics / Q000276:immunology; D003170:Complement Pathway, Alternative / Q000187:drug effects; D004195:Disease Models, Animal; D015870:Gene Expression; D005921:Glomerulonephritis / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D051379:Mice; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D044087:Receptor, Anaphylatoxin C5a / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D001324:Autoantigens; C488033:C5AR1 protein, human; D007155:Immunologic Factors; D044087:Receptor, Anaphylatoxin C5a; D015936:Complement C5a
keywords: ANCA-associated vasculitis; C5a; complement