title: Proteolysis of classic anti-neutrophil cytoplasmic autoantibodies (C-ANCA) by neutrophil proteinase 3.
abstract: C-ANCA, which are directed against neutrophil proteinase 3 (PR3), are specific markers for the diagnosis of active Wegener's granulomatosis (WG). The correlation between C-ANCA titre and WG disease activity suggests that these autoantibodies are involved in the development of WG. We have previously observed that C-ANCA interfere with PR3 proteolytic activity and with complexation of PR3 with its major physiologic inhibitor alpha 1-antitrypsin (alpha 1-AT). The possible pathogenic importance of C-ANCA may be related to the stability of C-ANCA IgG-PR3 complexes. In the present study we tested proteolysis by PR3 of human IgG and proteolysis of C-ANCA IgG complexed to the enzyme. All human IgG subclass proteins were cleaved by PR3. Digestion products were compared with those obtained by human neutrophil elastase (HNE)-mediated proteolysis of human IgG subclass proteins. Although cleavage products of similar size could be identified, the proteolytic activity of both enzymes towards human IgG differed. Furthermore, inhibiting C-ANCA IgG were cleaved into small peptides when complexed to PR3. The possible pathogenic consequences of these findings will be discussed.
authors.affiliation: Central Laboratory, Netherlands Red Cross Blood Transfusion Service, Amsterdam.
authors.forename: K M
authors.initials: KM
authors.lastname: Dolman
authors.forename: A
authors.initials: A
authors.lastname: Jager
authors.forename: A
authors.initials: A
authors.lastname: Sonnenberg
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; D000936:Antigen-Antibody Complex / Q000378:metabolism; D001323:Autoantibodies / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D007074:Immunoglobulin G / Q000378:metabolism*; D053146:Myeloblastin; D010446:Peptide Fragments / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D012697:Serine Endopeptidases / Q000502:physiology*
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D007074:Immunoglobulin G; D010446:Peptide Fragments; D011506:Proteins; D012697:Serine Endopeptidases; D053146:Myeloblastin