IgG class antibody to hepatic endothelial cell in sera of patients with autoimmune hepatitis and its pathophysiological significance

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An antibody against rat hepatic sinusoidal endothelial cells (HSECs) was identified in the serum of patients with autoimmune hepatitis (AIH). HSECs were isolated from rat liver, cultured for 18 h and fixed with glutaraldehyde. After incubation of the cells with 1 : 250 dilutions of serum from patients with AIH, chronic hepatitis type B or C, or normal healthy subjects, the amount of IgG bound was evaluated with peroxdaseconjugated protein A.In 14 of 15 patients with AIH, the amount of IgG bound to the cells exceeded the mean plus 3SD of normal healthy subjects and patients with chronic hepatitis type B and C.Treatment of the sera from AIH patients with dithiothreitol and iodoacetamide did not reduce the amount of IgG bound to HSECs. Furthermore, F(ab')2, prepared by peptic digestion of IgG from AIH patients, retained the activity to bind to HSECs. These findings indicate that the antigen determinant was a heparin-like structure on the surface of HSECs. The amount of IgG bound to the cells was significantly reduced after the patients were treated with corticosteroids. Culture of HSECs in the presence of IgG from AIH patients reduced the number of cells attached to the dish, suggesting that the antibody injured the cultured HSECs. From these results, the antibody against HSECs may contribute to the pathogenesis of AIH.