Antineutrophil cytoplasm antibodies and vasculitis

A link between ANCA titre and the degree of clinical activity in Wegener's granulomatosis has been suggested by both cross sectional and longitudinal studies. 4 11 In a prospective randomised study of 58 patients with Wegener's granulomatosis there were fewer clinical relapses and lower cumulative doses of prednisolone and cyclophosphamide in the group in which therapy was intensified on the basis of an increase in C-ANCA titre. 18 These results are encouraging but it would be premature to conclude that a rise in ANCA titre in a clinically stable patient should prompt an increase in immunosuppression, as this was a small study with only nine patients randomised to treatment, and a later report found an increase in ANCA titre to be neither a sensitive nor a specific marker of impending relapse.\n 37 38 This is consistent with the experience in adults in which an atypical pattern can be seen in a range of acute and chronic inflammatory conditions, and suggests that this pattern may be due to non-specific binding of antibody secondary to generalised immune activation and polyclonal B cell activation. In activated neutrophils, antigens recognised by ANCAs are redistributed to the cell surface and therefore are available to interact with circulating antibodies. 39 Exposure to ANCAs can cause activated neutrophils to degranulate, undergo an oxidative burst, and damage endothelial cells in culture. 40-42 Interaction of ANCAs with cytokine activated endothelial cells, which express the major C-ANCA antigen proteinase 3 on their surface, can increase neutrophil adhesion to the cells. 43 44 This may potentiate neutrophil mediated endothelial injury, with neutrophil derived agents released into the relatively sheltered microenvironment formed when the cells bind.