In vitro anti-mitochondrial antibody synthesis in patients with primary biliary cirrhosis.

Suppressor cell function was studied in 31 patients with primary biliary cirrhosis. Blood mononuclear cells were activated in vitro with suboptimal or optimal concentrations of concanavalin A and suppression of mitogen-induced proliferation or synthesis of anti-mitochondrial antibodies was measured. At suboptimal concentrations of concanavalin A, mean (+/- SE) suppression of proliferation by patients' cells was significantly less than 14 controls (18.7 +/- 5% vs 34.3 +/- 5%; P less than 0.005). The degree of suppressor activity correlated with the clinical disease, i.e., suppression was greater in patients with early than advanced disease. Spontaneous anti-mitochondrial antibody synthesis was not detected in cultures of mononuclear cells from normal subjects nor from patients with negative serum antibody, nor could it be induced by pokeweed mitogen in either group. In contrast, spontaneous anti-mitochondrial antibody synthesis was detected in cultures of 18/23 patients with positive serum antibody and was significantly augmented by pokeweed in 12/18. Anti-mitochondrial antibody synthesis was augmented by 48% (+/- 19) in response to pokeweed and concanavalin A-induced suppression higher (39.4 +/- 7%) in patients with low titer antibody compared to 1.6% (+/- 8) pokeweed augmentation and 5.5 +/- 3% concanavalin A-induced suppression in patients with high titer antibody. These results suggest that some patients with primary biliary cirrhosis have an immunoregulatory defect which expresses itself in part as an inability to regulate autoantibody synthesis.