basis the cases are defined autoimmune, in particular there Perinuclear anti-neutrophil cytoplasmic antibodies is no mention of the autoantibody profile. This is relevant (pANCA) have been recently defined as the most sensibecause it is fairly well accepted that AIH is not a unique tive autoantibody of type 1 autoimmune hepatitis (AIHentity. The classification recently proposed by Czaja and 1). Their prevalence in type 2 autoimmune hepatitis Manns 6 includes at least three types of AIH, each character-(AIH-2) has not yet been evaluated. The aim of the presized by distinct autoantibody markers as follows: high titre ent study was to verify the association of pANCA with smooth muscle antibody (SMA) and/or antinuclear antibody AIH-1 in an Italian series and to investigate the preva-(ANA) in type 1 (AIH-1), liver/kidney microsomal type 1 lence of the antibodies in AIH-2 and in proper control (LKM1) and/or liver cytosol type 1 (LC1) antibodies in type groups represented by cases of chronic hepatitis C (CH-2 (AIH-2), and soluble liver antigen antibody in type 3 (AIH-C) with similar autoimmune features. pANCA were 3). This immunopathological classification, although not acfound in 30 of 46 (65%) AIH-1 and in 4 of 30 (13%) ANA/ cepted by all hepatologists, allows comparison of data among smooth muscle antibody (SMA) positive CH-C (P Å different study groups and may influence the significance of .0000006). Nineteen AIH-2, 29 liver kidney microsomal new putative seroimmunological markers. antibody type 1/liver cytosol antibody type 1 (LKM1/LC1)A substantial proportion of ANA/SMA and LKM1/LC1 posipositive CH-C cases and 50 healthy controls were all negtive cases has evidence of concomitant hepatitis C virus infecative. In AIH-1, pANCA were significantly (P Å .009) more tion, at least in the Mediterranean area. 7,8 These intriguing frequent in males (8 of 9, 89%) than in females (22 of 37, cases are generally referred to as chronic hepatitis C (CH-C) 59%). All pANCA positive sera showed SMA of the antiwith autoimmune features and, although the term of unclasactin type. The present data confirm that pANCA, alsified chronic hepatitis as to viral or autoimmune origin has though less prevalent in our series than in other reports, been proposed, 9,10 we will use this current, less confusing do associate with AIH-1 also in the Mediterranean area jargon. Because no data are at present available concerning and show that it can identify a small subgroup (13%) of the prevalence of pANCA in these cases and in AIH type 2, ANA/SMA positive chronic hepatitis C, in which autoimthe present study was aimed both to validate the association mune reactions might play a more relevant role than of pANCA with AIH-1 in the Mediterranean area and to evalviral infection. They also show the antibodies are absent uate their occurrence in AIH-2 and in two groups of CH-C in AIH-2. In conclusion, pANCA appear to be mutually with identical autoantibodies. exclusive of LKM1 positivity, either hepatitis C virusrelated or not, thus representing a further val...

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Hepatitis C virus (HCV) antigens in liver biopsy have been detected by immunohistochemistry using both spontaneous human IgG and murine monoclonal or rabbit polyclonal monospecific reagents. Conflicting results have been obtained in different studies. This was probably because of the incapacity of single experimental antibodies, raised against synthetic or recombinant peptides, to recognize native tissue antigens. To overcome this possibility, we immunopurified monospecific spontaneous polyclonal human Ig, therefore induced by native antigens, from the single antigen-containing bands of RIBA 3 strips. Antibodies to c100, c33, c22, and NS5 antigens were obtained from the serum of a patient affected by chronic hepatitis C. The IgG fraction of this serum had proved to stain tissue HCV antigens. Eight biopsies were selected on the basis of strong hepatocellular reactivity with the whole IgG fraction in a variable number (from 5% to 75%) of cells. The four antigens were detected in all biopsies; a clear cellular codistribution was observed on serial sections. These data demonstrate that the possibility to identify HCV antigens in liver biopsies is higher when using human antibodies induced by native antigens rather than experimental antibodies. The approach of immunopurification of human antibodies can be extended to other HCV-related epitopes to obtain reagents useful for the selection and optimization of monoclonal or polyclonal antibodies.

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