Dolman K M, Jager A, Sonnenberg A, von dem Borne A E, Goldschmeding R
Central Laboratory, Netherlands Red Cross Blood Transfusion Service, Amsterdam.
Clin Exp Immunol. 1995 Jul;101(1):8-12. doi: 10.1111/j.1365-2249.1995.tb02269.x.
C-ANCA, which are directed against neutrophil proteinase 3 (PR3), are specific markers for the diagnosis of active Wegener's granulomatosis (WG). The correlation between C-ANCA titre and WG disease activity suggests that these autoantibodies are involved in the development of WG. We have previously observed that C-ANCA interfere with PR3 proteolytic activity and with complexation of PR3 with its major physiologic inhibitor alpha 1-antitrypsin (alpha 1-AT). The possible pathogenic importance of C-ANCA may be related to the stability of C-ANCA IgG-PR3 complexes. In the present study we tested proteolysis by PR3 of human IgG and proteolysis of C-ANCA IgG complexed to the enzyme. All human IgG subclass proteins were cleaved by PR3. Digestion products were compared with those obtained by human neutrophil elastase (HNE)-mediated proteolysis of human IgG subclass proteins. Although cleavage products of similar size could be identified, the proteolytic activity of both enzymes towards human IgG differed. Furthermore, inhibiting C-ANCA IgG were cleaved into small peptides when complexed to PR3. The possible pathogenic consequences of these findings will be discussed.
抗中性粒细胞胞浆抗体（C-ANCA）针对中性粒细胞蛋白酶3（PR3），是诊断活动性韦格纳肉芽肿（WG）的特异性标志物。C-ANCA滴度与WG疾病活动度之间的相关性表明，这些自身抗体参与了WG的发病过程。我们之前观察到，C-ANCA会干扰PR3的蛋白水解活性以及PR3与其主要生理抑制剂α1-抗胰蛋白酶（α1-AT）的结合。C-ANCA可能的致病重要性可能与其IgG-PR3复合物的稳定性有关。在本研究中，我们测试了PR3对人IgG的蛋白水解作用以及与该酶复合的C-ANCA IgG的蛋白水解作用。所有人类IgG亚类蛋白均被PR3切割。将消化产物与人中性粒细胞弹性蛋白酶（HNE）介导的人IgG亚类蛋白蛋白水解产物进行比较。尽管可以鉴定出大小相似的切割产物，但两种酶对人IgG的蛋白水解活性有所不同。此外，与PR3复合时，抑制性C-ANCA IgG被切割成小肽。将讨论这些发现可能的致病后果。
