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. 1992 Dec;90(3):409–414. doi: 10.1111/j.1365-2249.1992.tb05860.x

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

B A van de Wiel 1, K M Dolman 1, C H van der Meer-Gerritsen 1, C E Hack 1, A E von dem Borne 1, R Goldschmeding 1
PMCID: PMC1554581  PMID: 1458677

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.

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Selected References

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