Antiproteinase 3 antineutrophil cytoplasmic antibodies and disease activity in Wegener granulomatosis.

Background: The utility of antineutrophil cytoplasmic antibody (ANCA) levels to guide the management of patients with Wegener granulomatosis remains controversial.

Objective: To determine whether pro-proteinase 3 (PR3)-ANCA levels are a better measure of disease activity than mature-PR3-ANCA levels, whether decreases in either level are associated with shorter time to remission, and whether increases are followed by relapse.

Design: Prospective, observational cohort study.

ANCA are detectable in nearly all patients with active severe Wegener's granulomatosis.

Background: The pathogenic significance of antineutrophilic cytoplasmic antibodies (ANCA) in Wegener's granulomatosis is controversial. Their presence is influenced by the extent, severity, and activity of the disease at the time of sampling. The objective of this study was to determine the frequency of ANCA in patients with active Wegener's granulomatosis and to assess the influence of disease severity on test results.

Functional significance of Asn-linked glycosylation of proteinase 3 for enzymatic activity, processing, targeting, and recognition by anti-neutrophil cytoplasmic antibodies.

Proteinase 3 (PR3) is a neutral serine protease stored in neutrophil granules. It has substantial sequence homology with elastase, cathepsin G and azurocidin. PR3 is the target antigen for autoantibodies (ANCA) in Wegener's granulomatosis, a necrotizing vasculitis syndrome.

A novel capture-ELISA for detection of anti-neutrophil cytoplasmic antibodies (ANCA) based on c-myc peptide recognition in carboxy-terminally tagged recombinant neutrophil serine proteases.

Testing for antineutrophil cytoplasmic antibodies (ANCA) reacting with proteinase 3 (PR3) is part of the routine diagnostic evaluation of patients with small vessel vasculitis. For PR3-ANCA detection, capture ELISAs are reported to be superior to direct ELISAs. Standard capture ELISAs, in which PR3 is anchored by anti-PR3 monoclonal antibodies (moAB), have two potential disadvantages.

Differences between human proteinase 3 and neutrophil elastase and their murine homologues are relevant for murine model experiments.

Direct comparisons of human (h) and murine (m) neutrophil elastase (NE) and proteinase 3 (PR3) are important for the understanding and interpretation of inflammatory and PR3-related autoimmune processes investigated in wild-type-, mNE- and mPR3/mNE knockout mice. To this end, we purified recombinant mPR3 and mNE expressed in HMC1 and 293 cells and compared their biophysical properties, proteolytic activities and susceptibility to inhibitors with those of their human homologues, hPR3 and hNE. Significant species differences in physico-chemical properties, substrate specificities and enzyme kinetics towards synthetic peptide substrates, oxidized insulin B chain, and fibrinogen were detected.

Effects of carboxy-terminal modifications of proteinase 3 (PR3) on the recognition by PR3-ANCA.

Background: Autoantibodies directed against neutrophil proteinase 3 (PR3-ANCA) from patients with Wegener's granulomatosis and microscopic polyangiitis recognize conformational epitopes of PR3. During maturation of neutrophils, PR3 undergoes amino-terminal and carboxy-terminal processing. In contrast to amino-terminal processing, the effects of carboxy-terminal processing on recognition of PR3 by PR3-ANCA remain unknown.