RELEVANCE OF CLASSIC ANTINEUTROPHIL CYTOPLASMIC AUTOANTIBODY (C-ANCA)-MEDIATED INHIBITION OF PROTEINASE 3-ALPHA-1-ANTITRYPSIN COMPLEXATION TO DISEASE-ACTIVITY IN WEGENER-GRANULOMATOSIS

In the sera of patients with Wegener's granulomatosis (WG), C-ANCA can be detected that are directed against proteinase 3 (PR3). We have pre viously observed that C-ANCA interfere with PR3 proteolytic activity a nd with complexation of PR3 with its major physiologic inhibitor, alph a1-antitrypsin (alpha1AT). In the present study we investigated whethe r this inhibitory effect of C-ANCA on PR3-alpha1AT complexation correl ates with clinical activity of WG. Serial serum samples of eight conse cutive patients with histologically proven relapses of WG were tested. At the moment of relapse all sera revealed inhibitory activity toward s PR3-alpha1AT complexation (median 22%, range 10-59%). Disease activi ty 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-alpha1AT complexation , while they did not correlate with the C-ANCA titre detected by indir ect immunofluorescence (IIF) nor with IgG anti-PR3 antibody level meas ured by ELISA. The inhibitory effect of C-ANCA on PR3-alpha1AT complex ation had risen significantly at the moment of relapse compared with v alues 3 months (P<0.05) and 6 months (P<0.01) before relapse. Eight pa tients with established WG and positive for C-ANCA but without clinica l evidence of relapse served as controls. In this group no inhibitory effect of C-ANCA on PR3-alpha1AT complexation was observed in 7/8 pati ents sera. Sera of one control patient contained moderate C-ANCA inhib itory activity towards PR3-alpha1AT complexation, which remained at a constant level during the 6 months period of observation. Thus, diseas e activity in WG appears to be more closely related to C-ANCA inhibito ry activity towards PR3-alpha1AT complexation.