Open AccessInterference of Wegener's granulomatosis autoantibodies with neutrophil Proteinase 3 activity
Author(s) -
WIEL B. A.,
DOLMAN K. M.,
MEERGERRITSEN C. H.,
HACK C. E.,
BORNE A. E. G.,
GOLDSCHMEDING R.
Publication year - 1992
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1111/j.1365-2249.1992.tb05860.x
Subject(s) - proteinase 3 , autoantibody , immunology , medicine , antibody
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 alpha 1 ‐antitrypsin (α 1 AT). 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 α 1 AT (median 58.8% inhibition). Moreover, addition of purified PR3 to C‐ANCA‐positive sera from WG patients yielded less complexes with α 1 AT (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.