ANTINEUTROPHIL NUCLEAR ANTIBODIES (ANNA) IN PRIMARY BILIARY-CIRRHOSIS- THEIR PREVALENCE AND ANTIGEN-SPECIFICITY

Antineutrophil cytoplasmic antibodies (ANCA) are a group of autoantibo dies first associated with Wegener's granulomatosis (WG). In autoimmun e liver diseases, ANCA have been described recently in patients with p rimary biliary cirrhosis (PBC), autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC). Controversy exists about the prevalence and specificity of ANCA in patients with autoimmune liver diseases. T he purpose of this study was first to assess the prevalence of antineu trophil antibodies in patients with primary biliary cirrhosis and seco nd to identify possible target antigens of antineutrophil antibodies. Sera from 33 patients with PBC, 75 patients with NH, 16 patients with PSC, 90 control sera (chronic hepatitis B, chronic hepatitis C, alcoho lic liver cirrhosis, systemic lupus erythematosus) and sera from healt hy blood donors were enrolled in the present study. ANA and ANCA were detected using standard protocols, antibodies against the nuclear anti gen SP100 were detected by ELISA with recombinant antigen, antibodies against neutrophil alpha-granules were detected by ELISA. P-ANCA were found in two of 33 PBC sera, both patients presented with PBC/AIH over lap syndrome. In six of 33 (18%) PBC sera a nuclear dot like immunoflu orescence pattern (antineutrophil nuclear antibodies, ANNA) was observ ed. These dots were small in size and located all over the nucleus, th e anti-SP100 fluorescence. This result was confirmed by IFT on HEp-2 c ells and by ELISA. High titer antibodies against SP100 were found to b e specific for patients with PBC. Comparing the IFT results on Hep-2 c ells and human neutrophils, we found an excellent correlation (Spearma n's rank correlation coefficient = 0.968, P < 0.001). ANCA were detect ed in AIH type-1 (75%), SLA-positive AIH (36%) and PSC (63%). NH type- 2 was found to be ANCA negative. AU PSC sera contained no antibodies a gainst neurophil alpha-granules. Our results show: 1. P-ANCA in patien ts with PBC indicate a PBC/AIH overlap syndrome; 2. ANNA in patients w ith PBC are mostly directed against SP100; 3. neutrophil granule compo nents are not the ANCA specific antigens in patients with PSC.