ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES (ANCA) - THEIR DETECTION AND SIGNIFICANCE - REPORT FROM WORKSHOPS

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 disting uished by the patterns they produce by indirect immunofluorescence whe n tested on normal ethanol-fixed neutrophils. Diffuse fine granular cy toplasmic fluorescence (cANCA) is typically found in Wegener's granulo matosis, in some cases of microscopic polyarteritis and Churg Strauss syndrome, and in some cases of crescentic and segmental necrotising gl omerulonephritis, but it is rare in other conditions. The target antig en in usually proteinase 3. Perinuclear fluorescence (pANCA) is found in many cases of microscopic polyarteritis and glomerulonephritis. The se antibodies are often directed against myeloperoxidase but other tar gets include elastase, cathepsin G, lactoferrin, lysozyme and beta-glu curonidase. The third group designated ''atypical'' ANCA includes neut rophil 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 p attern on alcohol-fixed neutrophils result in cytoplasmic fluorescence when formalin acetone fixation is used. pANCA or atypical or primary sclerosing cholangitis, and they are found in a third of patients with Crohn's disease. The reported incidence of ANCA in rheumatoid arthrit is and SLE varies considerably but the patterns are predominantly pANC A and atypical ANCA. Where ANCA are associated with a small vessel vas culitis, such as Wegener's granulomatosis and microscopic polyarteriti s, antibody litres 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 presen ce of a vasculitis. ANCA are also common in HIV infections where all f luorescence patterns are found, but the presence of these antibodies h as no clinical significance. There have been many reports of ANCA occu rring occasionally in other diseases. ANCA have not yet been demonstra ted to be pathogenetic in the small vessel vasculitides. However there is in vitro evidence for 2 mechanisms, one of which focuses on neutro phil activation as the primary event and the other on antibody binding to vascular endothelium. Both mechanisms assume increased levels of c irculating tumor necrosis factor or another cytokine that might result from the infections that often precede the onset of Wegeners granulom atosis and microscopic polyarteritis. Successful new regimens in the t reatment of Wegener's granulomatosis and microscopic polyarteritis inc lude the use of pooled immunoglobulin, and cyclosporin in combination with low dose prednisolone, but one report of 3-weekly pulse cyclo-pho sphamide as a single agent indicated that it was effective in only 42% of patients.