Dolman K M, Stegeman C A, van de Wiel B A, Hack C E, von dem Borne A E, Kallenberg C G, Goldschmeding R
Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, Amsterdam.
Clin Exp Immunol. 1993 Sep;93(3):405-10. doi: 10.1111/j.1365-2249.1993.tb08192.x.
In the sera of patients with Wegener's granulomatosis (WG), C-ANCA can be detected that are directed against proteinase 3 (PR3). 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 1AT). In the present study we investigated whether this inhibitory effect of C-ANCA on PR3-alpha 1AT complexation correlates with clinical activity of WG. Serial serum samples of eight consecutive patients with histologically proven relapses of WG were tested. At the moment of relapse all sera revealed inhibitory activity towards PR3-alpha 1AT complexation (median 22%, range 10-59%). Disease activity score (r = 0.87, P < 0.02) and C-reactive protein (CRP) levels (r = 0.66, P < 0.1) correlated with C-ANCA inhibition of PR3-alpha 1AT complexation, while they did not correlate with the C-ANCA titre detected by indirect immunofluorescence (IIF) nor with IgG anti-PR3 antibody level measured by ELISA. The inhibitory effect of C-ANCA on PR3-alpha 1AT complexation had risen significantly at the moment of relapse compared with values 3 months (P < 0.05) and 6 months (P < 0.01) before relapse. Eight patients with established WG and positive for C-ANCA but without clinical evidence of relapse served as controls. In this group no inhibitory effect of C-ANCA on PR3-alpha 1AT complexation was observed in 7/8 patients sera. Sera of one control patient contained moderate C-ANCA inhibitory activity towards PR3-alpha 1AT complexation, which remained at a constant level during the 6 months period of observation. Thus, disease activity in WG appears to be more closely related to C-ANCA inhibitory activity towards PR3-alpha 1AT complexation.
在韦格纳肉芽肿（WG）患者的血清中，可检测到针对蛋白酶3（PR3）的C-ANCA。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（α1AT）的复合。在本研究中，我们调查了C-ANCA对PR3-α1AT复合的这种抑制作用是否与WG的临床活动相关。对八名经组织学证实有WG复发的连续患者的系列血清样本进行了检测。在复发时，所有血清均显示出对PR3-α1AT复合的抑制活性（中位数22%，范围10 - 59%）。疾病活动评分（r = 0.87，P < 0.02）和C反应蛋白（CRP）水平（r = 0.66，P < 0.1）与C-ANCA对PR3-α1AT复合的抑制作用相关，而它们与间接免疫荧光（IIF）检测的C-ANCA滴度以及ELISA测量的IgG抗PR3抗体水平均无相关性。与复发前3个月（P < 0.05）和6个月（P < 0.01）的值相比，在复发时C-ANCA对PR3-α1AT复合的抑制作用显著升高。八名确诊为WG且C-ANCA阳性但无复发临床证据的患者作为对照。在该组中，7/8患者的血清未观察到C-ANCA对PR3-α1AT复合的抑制作用。一名对照患者的血清对PR3-α1AT复合具有中等程度的C-ANCA抑制活性，在6个月的观察期内保持恒定水平。因此，WG中的疾病活动似乎与C-ANCA对PR3-α1AT复合的抑制活性更为密切相关。
