title: What is new with anti-neutrophil cytoplasmic antibodies: diagnostic, pathogenetic and therapeutic implications.
abstract: Anti-neutrophil cytoplasmic antibodies, as detected by indirect immunofluorescence, have limited diagnostic significance as they occur in a variety of inflammatory disorders. The presence of antibodies to defined target antigens of anti-neutrophil cytoplasmic antibodies, that is proteinase 3 and myeloperoxidase, is, however, highly specific for one of the systemic vasculitides, in particular Wegener's granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome, and idiopathic pauci-immune necrotizing crescentic glomerulonephritis. In general, anti-proteinase-3-positive patients show more widespread organ involvement, more granuloma formation, and a more severe initial course of their renal lesions than anti-myeloperoxidase-positive patients; however, there is considerable overlap, and either antibody specificity may be found in the different clinical syndromes. In vitro, anti-neutrophil cytoplasmic antibodies are able further to activate pre-activated neutrophils and monocytes, which can result in endothelial damage. A direct activating effect of anti-neutrophil cytoplasmic antibodies on endothelial cells has been suggested, but those studies should be confirmed. In vivo, experimental data support a pathogenetic role for anti-neutrophil cytoplasmic antibodies, particularly anti-myeloperoxidase, but besides anti-neutrophil cytoplasmic antibodies a second pro-inflammatory stimulus seems to be required to induce lesions. Whether anti-neutrophil cytoplasmic antibodies can be a direct target for treatment has still to be proved. Current immunosuppressive treatment regimens for the anti-neutrophil cytoplasmic antibody-associated vasculitides are, however, unsatisfactory because of side-effects, that is opportunistic infections and malignancies. New treatment regimens, based on new pathogenetic concepts, are currently being tested.
authors.affiliation: Department of Clinical Immunology, University Hospital, Groningen, The Netherlands. c.g.m.kallenberg@int.azg.nl
authors.forename: C G
authors.initials: CG
authors.lastname: Kallenberg
authors.forename: J W
authors.initials: JW
authors.lastname: Tervaert
mesh_terms: D000818:Animals; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000378:metabolism*; D003593:Cytoplasm / Q000276:immunology; D014890:Granulomatosis with Polyangiitis / Q000175:diagnosis / Q000276:immunology / Q000628:therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008954:Models, Biological; D053146:Myeloblastin; D009504:Neutrophils / Q000276:immunology; D009195:Peroxidase / Q000276:immunology; D012697:Serine Endopeptidases / Q000276:immunology; D014657:Vasculitis / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D007166:Immunosuppressive Agents; D009195:Peroxidase; D012697:Serine Endopeptidases; D053146:Myeloblastin