van de Wiel B A, Dolman K M, van der Meer-Gerritsen C H, Hack C E, von dem Borne A E, Goldschmeding R
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
Clin Exp Immunol. 1992 Dec;90(3):409-14. doi: 10.1111/j.1365-2249.1992.tb05860.x.
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.
经典抗中性粒细胞胞浆自身抗体（C-ANCA）是韦格纳肉芽肿（WG）的疾病特异性标志物。这些针对蛋白酶3（PR3）的自身抗体可能的致病作用尚不清楚。我们研究了C-ANCA对PR3蛋白水解活性以及PR3与α1-抗胰蛋白酶（α1AT）复合的影响。来自8例活动性WG患者的C-ANCA IgG显著抑制PR3蛋白水解活性，尤其是对弹性蛋白的活性（中位抑制率84.2%）。C-ANCA IgG显著抑制PR3与α1AT的复合（中位抑制率58.8%）。此外，与含有核周抗中性粒细胞胞浆自身抗体（P-ANCA）的血清或ANCA阴性血清相比，向WG患者的C-ANCA阳性血清中添加纯化的PR3后，与α1AT形成的复合物较少（中位44.8%）。这些发现表明C-ANCA存在一种迄今未知的特性，这可能在WG的发病机制中具有重要意义。
