ACTIVATION OF GRANULOCYTES BY ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES (ANCA) IN WEGENERS GRANULOMATOSIS - A PREDOMINANT ROLE FOR THE IGG3 SUBCLASS OF ANCA

To study ANCA-induced granulocyte activation in relation to disease activity in Wegener's granulomatosis (WG), serum samples taken from patients with WG at the time of active (n=17) and inactive (n=17) disease were analysed for their capacity to activate primed normal donor granulocytes. Compared with control sera (n=6), the capacity of IgG fractions from patients with WG to induce the respiratory burst was significantly higher (P<0.0001). Furthermore, the capacity to induce the respiratory burst significantly correlated with ANCA titre (r=0.499, P=0.003). IgG fractions from patients with active extensive disease induced the respiratory burst significantly more stongly than IgG fractions from patients with limited disease (n=7) (P<0.01) or patients during disease remission (n=17) (P<0.001). As ANCA-induced neutrophil activation is Fc-dependent and different IgG subclasses are involved in the interaction with various Fc receptors from neutrophils, we assessed changes in ANCA titre, total IgG and IgG subclass distribution of ANCA during active disease and remission in relation to the neutrophil-activating capacity of ANCA. Changes in capacity to activate granulocytes were related neither to changes in titre nor to changes in levels of total IgG, IgG1, IgG3, or IgG4 subclass of ANCA. However, changes in capacity to induce the respiratory burst were significantly related to changes in the relative amount of the IgG3 subclass of ANCA (P<0.001), and not to changes in the relative amount of IgG1 or IgG4 subclass of ANCA. These data suggest that the increase in neutrophil-activating capacity of ANCA from inactive to active disease is, at least in part, based on the relative increase of the IgG3 subclass of ANCA that occurs during active disease.