Anti-neutrophil cytoplasmic antibodies in patients with chronic liver diseases: Prevalence, antigen specificity and predictive value for diagnosis ofautoimmune liver disease

Background: Anti-neutrophil cytoplasmic antibodies (ANCA) against proteinas e 3 are diagnostic of Wegener's granulomatosis, but ANCA occur also in pati ents with other inflammatory disorders, such as ulcerative colitis, primary sclerosing cholangitis (PSC) and autoimmune hepatitis. As their predictive value for autoimmune liver disease remains unknown, we analysed the preval ence and antigen specificity of ANCA in patients with various chronic liver diseases (CLD). Methods: We studied sera from 100 patients with primary biliary cirrhosis ( PBC), from 76 with PSC and from 279 with various CLD, consecutively drawn d uring a 5-year period at the time of liver biopsy. The ANCA were detected b y indirect immunofluorescence (IIF) while the antigen specificity was chara cterized by ELISA by using lactoferrin, neutrophil elastase, cathepsin G an d BPI (bactericidal/permeability increasing protein) as antigens. Results: In PBC, ANCA were detected by IIF in 39 patients (39%). The antige n reactivity by ELISA was lactoferrin in seven, elastase in 15, BPI in 20 a nd cathepsin G in four patients. Four patients had reactivity against more than one antigen. In PSC, IIF demonstrated ANCA in 49 patients (65%). The a ntigen reactivity was lactoferrin in 17, elastase in 14, BPI in 20 and cath epsin G in four patients. Twelve patients showed reactivity against more th an one antigen. In CLD, ANCA were observed in sera from 55 patients (20%). Nineteen of 45 patients (42%) with autoimmune liver disease were ANCA posit ive versus 36/234 (15%) with non-autoimmune liver disease (P = 0.0002). Amo ng IIF-positive patients, antibody reactivity against lactoferrin was noted in 14, elastase in 28, BPI in 25 and cathepsin G in five patients. Twenty- one patients had reactivity against more than one antigen. Elastase and BPI antibodies occurred more frequently in patients with autoimmune compared t o non-autoimmune liver disease (P < 0.01). Conclusions: Anti-neutrophil cytoplasmic antibodies are prevalent in patien ts with chronic liver diseases, but although they occur more frequently in patients with autoimmune liver disease their specificity and sensitivity fo r autoimmune liver disease is low. The predominant antigens are lactoferrin , elastase and BPI, but the correlation between IIF findings and ELISA reac tivity against these antigens is weak. (C) 2000 Blackwell Science Asia Pty Ltd.