The antigenic significance and methods of detection of the anti-neutrophil cytoplasmic autoantibodies (ANCA).

Introduction Systemic vasculitis is often difficult to diagnose. The recent discovery of a new class of auto-antibodies, the anti-neutrophil cytoplasmic auto-antibodies (ANCA), provides clinicians with a serological test strongly supportive of the diagnosis of the commonest forms of systemic necrotizing vasculitis. ANCA are IgG autoantibodies specific for different constituents of neutrophil azurophilic granules and monocyte lysosomes. These anti-bodies are the first serological markers for several forms ofsystemic vasculitis, particularly Wegener's granulomatosis and polyarteritis nodosa, as well as for the commoner types of necrotizing and crescen-tic glomerulonephritis.' In addition to their recognized use in the diagnosis and follow-up of these conditions, it appears that ANCA may be a pathogenic factor inducing vascular injury in patients with ANCA-associated disease. This suspicion arises from in vitro evidence that ANCA are capable of activating neutrophils causing the release of lytic proteases and toxic oxygen radicals.2 The existence of autoantibodies against neutro-phils has been known for almost 30 years. A granulocyte-specific antinuclear factor was reported in 1964.3 Eight years later, Wiik and Mun-the4 described a standardized method for the detection of granulocyte-specific anti-nuclear antibodies (GS-ANA). These investigators performed an indirect immunofluorescence (IIF) procedure on ethanol-fixed neutrophils, which remains the standard technique for ANCA detection today. GS-ANA were found to be specific for neutrophil and monocyte nuclei, did not react with lymphocytes, and were mainly detected in patients with rheumatic diseases, especially rheumatoid arthritis and Felty's syndrome, as well as in some patients with ulcerative colitis. Cytoplasmic immunostaining pattern of gran-ulocytes (c-ANCA) was reported in 1982 in eight patients with segmental necrotizing glomerulo-nephritis.5 Later, four further patients with vas-culitis, glomerulonephritis and the serum presence of c-ANCA were reported.6 It was only in 1985 when van der Woude et al.7 noticed that c-ANCA mainly occurred in patients with Wegener's granulomatosis, that interest in these antibodies became intense. In addition, Falk and Jennette8 recognized in 1988 the clinical importance of the perinuclear immunostaining of neutrophils (p-ANCA) as well as its association with myeloperox-idase (MPO). They demonstrated that this was an artifactual pattern of cell fixation with ethanol and found these antibodies mainly in patients with idiopathic necrotizing and crescentic glomerulo-nephritis. It is now well accepted that ANCA have two main antigenic specificities each one of them associating with two main clinical disorders. Thus, the c-ANCA mainly represent anti-proteinase 3 (PR3) antibodies which mostly identify patients with biopsy-proven Wegener's granulomatosis. The p-ANCA represent anti-MPO antibodies which are mainly seen …