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© Dirk Biddle
Anti-neutrophil cytoplasmic antibodies (ANCA) have been found to be associated with some types of vasculitis. ANCA are specific antibodies (IgG1, 2, 3 and 4 subclasses) for antigens in the cytoplasmic granules of neutrophils and monocyte lysosomes (A saclike cellular organelle that contains various hydrolytic enzymes. (M+)). First reported in 1982, these antibodies can be detected with indirect immunofluorescence microscopy. Two major patterns of staining revealed two types of antibody; the cANCA (cytoplasmic) and the pANCA (perinuclear). More recently however enzyme-linked immunosorbent assay (ELISA) has been used to characterise ANCA and this method, deemed more specific and more clinically relevant than immunofluorescence microscopy, is able to identify the primary autoantigenic targets of cANCA as proteinase-3 (PR-3) and of pANCA as myeloperoxidase (MPO). These antibodies are often directed against myeloperoxidase but other targets include elastase, cathepsin G, lactoferrin, lysozyme and β-D-glucuronidase. However, the terms proteinase-3-ANCA (PR3-ANCA) and myeloperoxidase--ANCA (MPO--ANCA) are now in use. There is a third ANCA group, designated ''atypical'', that includes neutrophil nuclear fluorescence and some unusual cytoplasmic patterns and while a few of the target antigens are shared with pANCA, the others have not been identified yet (1).
The link between ANCA and the pathogenesis of ANCA-associated disease is unknown, but it is postulated that neutrophils and mononuclear phagocytes are directly activated by ANCA and these activated cells, in turn, attack vessel walls, producing injury similar to that produced by anti-glomular basement membrane antibodies or immune complexes (109a). Binding of ANCAs to neutrophils or monocytes in vitro stimulates the cells to undergo a respiratory burst that generates toxic oxygen metabolites, and to secrete pro-inflammatory mediators such as LTB4, IL-8, and MCP-1 which recruit more neutrophils and monocytes. The neutrophils also degranulate, releasing lytic enzymes which may injure the vascular endothelium. Whether this series of events occurs in vivo is less clearly defined (21). Glomerular involvement in immune complex vasculitis typically results in proliferative or membranoproliferative glomerulonephritis, whereas ANCA disease usually causes necrotizing glomerulonephritis with extensive crescent formation. Involvement of renal vessels other than glomerular capillaries is rare in immune complex vasculitis but common in ANCA vasculitis (2).
The different ANCA patterns are not entirely sensitive or specific for any particular form of vasculitis however cANCA is typically found in Wegener's granulomatosis, in some cases of Microscopic polyangiitis and Churg Strauss syndrome, and in some cases of crescentic and segmental necrotising glomerulonephritis, but is rare in other conditions. The target antigen is usually proteinase 3 (PR3). Perinuclear fluorescence (pANCA) is found in many cases of Microscopic polyarteritis, necrotizing and crescentic glomerulonephritis, Churg-Strauss syndrome, Polyarteritis nodosa, Wegener's granulomatosis, Systemic lupus erythematosis, Rheumatoid arthritis and Chronic IBD. pANCA are also found in a third of patients with Crohn's disease (3).
The incidence of ANCA in Micrscopic polyangiitis is PR3-ANCA (40%), MPO-ANCA (50%) and negative (10%). In Wegener’s garanulomatosis the incidence is PR3-ANCA (75%), MPO-ANCA (20%) and negative (5%). For Churg-Strauss syndrome it is PR3-ANCA (10%), MPO-ANCA (60%) and negative (30%) (320a). The reported incidence of ANCA in rheumatoid arthritis and Systemic lupus erythematosus varies considerably but the patterns are predominantly pANCA and atypical ANCA (1).
While much has been made of ANCA and its association with certain vasculitides, it remains clear that their absence in many patients suggests that at least in their currently described form, they are not a necessary requirement for the presence of any particular vasculitis syndrome.
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1. http://nic.sav.sk/logos/books/scientific/node18.html#SECTION00433300000000000000
2. http://cnserver0.nkf.med.ualberta.ca/cn/Schrier/Volume4/chapter2/ADK4-02_4-6.pdf
3. http://www.thedoctorsdoctor.com/diseases/anca.htm
Testing information: http://www.aruplab.com/guides/clt/tests/clt_106b.jsp#1143318
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