Neutrophil antibodies (pANCA) in chronic liver disease and inflammatory bowel disease: do they react with different antigens?

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Abstract
A high frequency of perinuclear neutrophil antibodies (pANCA) has been described in patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC). We evaluated the presence of pANCA in chronic liver disease and compared the immunoglobulin G (IgG) subclasses of pANCA in inflammatory bowel disease with chronic liver disease. Since the antigen reacting with pANCA could not be determined, the antigenic role of various neutrophil antigens was evaluated. Detection of pANCA and their IgG subclass was performed by immunofluorescence. One hundred and forty patients with chronic liver disease, 96 patients with inflammatory bowel disease and 40 healthy controls were tested for pANCA. pANCA positive and negative sera were evaluated for their reactivity with different neutrophil antigens in an enzyme-linked immunosorbent assay (ELISA) system. pANCA were found in 8 of 23 patients (35%) with autoimmune hepatitis, in 6 of 21 patients (28%) with primary biliary cirrhosis (PBC), in 18 of 25 patients (72%) with PSC, in 3 of 48 patients (6%) with viral hepatitis, in 30 of 48 patients (62%) with UC, and in 2 of 48 patients (4%) with Crohn's disease. All 20 patients with alcoholic liver disease and 40 healthy controls were negative for pANCA. In contrast to the patients with UC who had 83% IgG1 and only 13% IgG3 antibodies, patients with PSC and PBC had an overexpression of IgG3 antibodies (PSC: 50% IgG3; PBC: 67% IgG3). A proportion of pANCA positive sera recognized lactoferrin, myeloperoxidase, cathepsin G, laminarase and alpha 1-antitrypsin. pANCA is not present only in patients with UC but in autoimmune liver diseases such as PSC, autoimmune hepatitis and PBC. Considering the IgG subclass of pANCA, the antibody response of patients with UC is different from patients with liver disease. No unique pANCA specific antigen could be detected, so heterogeneity of pANCA has to be considered.

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