title: Interference of Wegener's granulomatosis autoantibodies with neutrophil Proteinase 3 activity.
abstract: Classic anti-neutrophil cytoplasmic autoantibodies (C-ANCA) are disease-specific markers of Wegener's granulomatosis (WG). The possible pathogenetic role of these autoantibodies, which are directed against Proteinase 3 (PR3), is not yet clear. We studied the effect of C-ANCA on PR3 proteolytic activity and on the complexation of PR3 with alpha 1-antitrypsin (alpha 1AT). C-ANCA IgG from eight patients with active WG significantly inhibited PR3 proteolytic activity, particularly towards elastin (median 84.2% inhibition). C-ANCA IgG significantly inhibited the complexation of PR3 with alpha 1AT (median 58.8% inhibition). Moreover, addition of purified PR3 to C-ANCA-positive sera from WG patients yielded less complexes with alpha 1AT (median 44.8%) compared with sera containing perinuclear anti-neutrophil cytoplasmic autoantibodies (P-ANCA) or ANCA-negative sera. These findings indicate the existence of a hitherto unknown property of C-ANCA, which may be of importance in the pathogenesis of WG.
authors.affiliation: Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
authors.forename: B A
authors.initials: BA
authors.lastname: van de Wiel
authors.forename: K M
authors.initials: KM
authors.lastname: Dolman
authors.forename: C H
authors.initials: CH
authors.lastname: van der Meer-Gerritsen
authors.forename: C E
authors.initials: CE
authors.lastname: Hack
authors.forename: A E
authors.initials: AE
authors.lastname: von dem Borne
authors.forename: R
authors.initials: R
authors.lastname: Goldschmeding
mesh_terms: D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies / Q000097:blood / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D014890:Granulomatosis with Polyangiitis / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D053146:Myeloblastin; D009504:Neutrophils / Q000201:enzymology; D010196:Pancreatic Elastase / Q000097:blood; D012697:Serine Endopeptidases / Q000378:metabolism*; D000515:alpha 1-Antitrypsin / Q000378:metabolism
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies; D015415:Biomarkers; D007074:Immunoglobulin G; D000515:alpha 1-Antitrypsin; D012697:Serine Endopeptidases; D010196:Pancreatic Elastase; D053146:Myeloblastin