Mechanism of hepatocyte injury in autoimmune hepatitis : involvement of hepatic sinusoidal endothelial cell injury.

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There have been several lines of evidence indicating that antibody-dependent cell-mediated cytotoxicity (ADCC) is involved in the development and perpetuation of hepatocyte injury in autoimmune hepatitis (AIH). Using rat hepatic sinusoidal endothelial cells as the substrate, we looked for the antibody to these cells in the sera of patients with chronic liver diseases. The antibody was detected in 97.1% of AIH patients examined. In the patients with chronic hepatitis (CH) B,CH-C and primary biliary cirrhosis, the positivity rates were 7.9,5.9 and 13.0%, respectively. Thus the occurrence of the antibody charactrized AIH.We also found that the antibody was cytotoxic to hepatic sinusoidal endothelial cells, suggesting that the endothelial cell injury by this antibody induced micro-circulatory disturbance, leading to hepatocyte injury. Incubation of F(ab')_2 from sera of patients with bovine carotid artery endothelial cell, not with rat hepatocyte and dRLh84 cell, diminished the reactivity with hepatic sinusoidal endothelial cell, suggesting that the antibody recognized the endothelial cell-specific antigen. The antibody was also detected when human umblical vascular endothelial cell and human hepatic sinusoidal endothelial cell was used as the substrate. We reported the occurrence of antisulfatide antibody in sera of patients with autoimmune hepatitis. The antisulfatide antibody was cross-reactive with heparin, suggesting that this antibody was reactive with the endothelial cell and the same as the antibody to endothelial cell.