HETEROGENEITY OF LIVER-KIDNEY MICROSOMAL ANTIBODY TYPE-1 IN AUTOIMMUNE HEPATITIS AND HEPATITIS-C VIRUS-RELATED LIVER-DISEASE

Liver/kidney microsomal antibody type 1 (LKM-1), the serological marke r of a subset of autoimmune hepatitis, is also present in a proportion of patients with hepatitis C virus (HCV) related chronic liver diseas e. To characterise further this autoreactivity and to evaluate whether an autoantibody giving an identical immunofluorescence staining, and detected in two different clinical conditions, involves the same antig enic target(s), sera from autoimmune and HCV infected patients were te sted with native, recombinant, and synthetic antigens. Sixty five sera were selected on the basis of the typical immunofluorescence pattern: 50 patients had serological markers of HCV infection, the remaining 1 5 suffered from autoimmune hepatitis. The reactivity of each serum wit h rat and human microsomal fractions, full length human recombinant CY P2D6, and two synthetic peptides spanning the amino acid regions 257-2 69 and 373-398 of CYP2D6 was systematically investigated by immunoblot ting. Fourteen (93%) sera from autoimmune hepatitis patients and 39 (7 8%) from HCV infected patients reacted with rat and/or human microsoma l polypeptides of 39 kD, 50 kD, 58 kD, and 66 kD in different associat ions, the 50 kD band being the most frequently observed. Reactivity to CYP2D6 and its amino acid sequence 257-269 was significantly more com mon in autoimmune hepatitis than in HCV infected patients (p < 0.001 a nd p < 0.0003, respectively). LKM-1 reactivity is directed against het erogeneous and not entirely defined autoantigens. The main target in a utoimmune sera is CYP2D6 and its 257-269 amino acid region, while sera from patients with HCV infection are more likely to recognise other m icrosomal targets, the molecular identity of which is currently unknow n.