Interference of Wegener's granulomatosis autoantibodies with neutrophil Proteinase 3 activity

SUMMARY 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 complcxation of PR3 with alpha1‐antitrypsin (α1AT). 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 α1AT (median 58.8% inhibition). Moreover, addition of purified PR3 to C‐ANCA‐positive sera from WG patients yielded less complexes with α1AT (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.