Wegener's granulomatosis and anti-neutrophil cytoplasm antibodies(ANCA).

Abstract

Recently, the detection of anti-neutrophil cytoplasm antibodies (ANCA) has gained worldwide acceptance as an important, additional diagnostic tool in respect to vasculitic and granulomatous syndromes such as Wegener's granulomatosis (WG). The classical ANCA, C-ANCA, which is primarily observed in WG, is defined by an indirect immunofluorescence (IIF) technique yielding an irregular, granular staining of the cytoplasm of neutrophils and monocytes using smeared, alcohol-fixed human leucocytes as substrate. The C-ANCA related antigen is a 29 kD molecule (possibly Proteinase 3), which is retrieved from the azurophil granules of the neutrophils. An enzyme linked immunosorbent assay (ELISA), using azurophil granules as substrate, has proven to correlate well with the IIF assay. Using both assays simultaneously increases the specificity and sensitivity of C-ANCA detection.A group of patients with vasculitis and glomerulonephritis has autoantibodies against myeloperoxidase (MPO-ANCA). These sera yield an artifactual, perinuclear IIF staining (P-ANCA) distinct from the C-ANCA staining. As perinuclear IIF staining may be due to several autoantibodies, MPO-ANCA must be identified by ELISA.Detection of C-ANCA has made it possible to identify patients with WG earlier in the course of disease and has increased the number of patients identified by a factor 3. C-ANCA is negative in cases with polymorphic reticulosis, lymphomas and sarcoidosis. C-ANCA often disappears when WG is brought in remission and reappears before and during relapses. In untreated, active cases of WG, C-ANCA can be detected in 50-95% of cases depending on organ manifestations while MPO-ANCA may be detected in 15% of cases with WG and kidney involvement.A possible pathogenetic role of C-ANCA and P-ANCA has been suggested by the finding that the addition of purified IgG-ANCA to healthy neutrophils in vitro causes activation of these cells. As the circulating neutrophils are not activated, the disease modulating mechanism in WG must be further explored. The detection of ANCA, however, is an important clue to the nature of autoimmune diseases and the rapid development in this particular field of research holds great promise for the future.