Anti-neutrophil cytoplasmic antibodies (ANCA) are antibodies directed against enzymes that are found mainly within the azurophil or primary granules of neutrophils. There are 3 types of ANCA that can be distinguished by the patterns they produce by indirect immunofluorescence when tested on normal ethanolfixed neutrophils. Diffuse fine granular cytoplasmic fluoresence (cANCA) is typically found in Wegener's granulomatosis, in some cases of microscopic polyarteritis and Churg Strauss syndrome, and in some cases of crescentic and segmental necrotising glomerulonephritis, but it is rare in other conditions. The target antigen is usually proteinase 3. Perinuclear fluorescence (pANCA) is found in many cases of microscopic polyarteritis and in other cases of crescentic and segmental necrotising glomerulonephritis. These antibodies are often directed against myeloperoxidase but other targets include elastase, cathepsin G, lactoferrin, lysozyme and beta-glucuronidase. The third group designated “atypical” ANCA 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. Sera that produce a pANCA or atypical ANCA pattern on alcohol-fixed neutrophils result in cytoplasmic fluorescence when formalin acetone fixation is used. pANCA or atypical ANCA occur in about 2/3 of all individuals with ulcerative colitis or primary sclerosing cholangitis, and they are found in a third of patients with Crohn's disease. The reported incidence of ANCA in rheumatoid arthritis and SLE varies considerably but the patterns are predominantly pANCA and atypical ANCA. Where ANCA are associated with a small vessel vasculitis, such as Wegener's granulomatosis and microscopic polyarteritis, antibody titres may parallel disease activity and have been used to monitor the response to treatment. In other non-vasculitic conditions ANCA levels do not necessarily reflect disease activity or the presence of a vasculitis. ANCA are also common in HIV infections where all fluorescence patterns are found, but the presence of these antibodies has no clinical significance. There have been many reports of ANCA occurring occasionally in other diseases.
ANCA have not yet been demonstrated to be pathogenetic in the small vessel vasculitides. However there is in vitro evidence for 2 mechanisms, one of which focuses on neutrophil activation as the primary event and the other on antibody binding to vascular endothelium. Both mechanisms assume increased levels of circulating tumor necrosis factor or another cytokine that might result from the infections that often precede the onset of Wegener's granulomatosis and microscopic polyarteritis.
Successful new regimens in the treatment of Wegener's granulomatosis and microscopic polyarteritis include the use of pooled immunoglobulin, and cyclosporin in combination with low dose prednisolone, but one report of 3-weekly pulse cyclophosphamide as a single agent indicated that it was effective in only 42% of patients.