Autoimmune reactivity of sera to hepatocyte plasma membrane in type 1 autoimmune hepatitis

Type 1 autoimmune hepatitis (AIH-1) is an organ-specific autoimmune liver d isease for which no tissue-specific autoantigen has yet been identified. We examined the reactivity by sensitive immunoblotting with enhanced chemilum inescence (IB-ECL) of 43 sera from patients with AIH-1 and 182 sera from pa tients with other diseases on hepatocyte plasma membrane derived from rat o r human liver (RHPM, HHPM) and separated by aqueous two-phase partition. Th e sera studied were from patients with AIH-1, primary biliary cirrhosis, ch ronic viral hepatitis, and systemic lupus erythematosus (SLE); and from nor mal subjects. Specificity of reactivity by IB-ECL was sought: (i) by testin g sera on human or rat liver membrane; (ii) by testing sera on liver or kid ney membrane; (iii) by serial titration of reactive sera; and (iv) by testi ng reactive sera from AIH-1 before and after successful treatment with pred nisolone. The results were that in AIH-1 there were multiple reactive compo nents which were not species-specific, since they were detected with both R HPM and HHPM, but were mostly tissue-specific for liver. There was no signi ficant correlation between antinuclear antibodies (ANA) titer and the frequ encies of sera reactivities against RHPM. Most of these reactive components were demonstrable at a lesser frequency in other liver diseases and in SLE . There was a striking decrease in reactivity by IB-ECL of AIH-1 sera with liver membrane after clinical remission, further suggesting that difference s between AIH-1 and other inflammatory liver diseases and SLE are predomina ntly quantitative rather than qualitative. However, our study did point to candidate liver membrane antigens with molecular sizes of 136, 116, 81, and 49 kDa, additional to components previously described by others. The molec ular identification of these prominent reactants with AIH-1 sera could prov e informative for ascertaining pathogenesis.