Evidence against antibody-dependent cell-mediated cytotoxicity as a possible mechanism of liver cell injury in cystic fibrosis.

Previous studies suggested that cell-mediated cytotoxicity may play a role in the pathogenesis of liver disease complicating cystic fibrosis (CF), possibly through an antibody-dependent mechanism (ADCC). In order to verify this hypothesis, sera from 23 CF patients with or without liver disease were incubated with isolated rabbit hepatocytes before exposure to normal peripheral blood mononuclear cells (PBMC), thus allowing any IgG reacting with liver cell membrane antigens to induce an ADCC reaction. A minimal increase in cytotoxicity was recorded using one of the 9 sera from patients with clinically apparent liver disease, whereas none of the 14 sera from CF patients without liver disease were able to induce significant ADCC. In contrast, sera from children with autoimmune chronic active hepatitis rendered rabbit hepatocytes susceptible to damage by normal PBMC. These results argue against a role for ADCC in the pathogenesis of liver disease associated with CF.