Genetic abnormalities of immunoregulation in primary biliary cirrhosis

Patients with primary biliary cirrhosis have an abnormality of lymphocyte suppressor cell function that could play a role in the pathogenesis of their disease. To investigate this possibility, suppressor cell function in patients with primary biliary cirrhosis, in their healthy first-degree relatives, in unrelated household contacts, in patients with other types of cirrhosis, and in normal control subjects was studied. The method used is based on the finding that the in vitro addition of concanavalin A to pokeweed mitogen-stimulated lymphocytes activates suppressor cells, which in turn inhibit immunoglobulin synthesis. Thirteen of 16 patients with primary biliary cirrhosis and six of 23 healthy relatives had significant impairment of IgG suppression. All six of these relatives were female. No abnormal suppression was found in unrelated household contacts of patients with primary biliary cirrhosis, in patients with other types of cirrhosis, or in healthy control subjects. There was no correlation between results of the IgG suppressor cell assay and the disease activity in patients with primary biliary cirrhosis. These data suggest that the abnormal suppressor cell function is not a direct cause of primary biliary cirrhosis; however, it may be a genetic marker for susceptibility to this disease.