Complement activation in primary biliary cirrhosis: an in vitro model.

Increased concentrations of C3dg were demonstrated in plasma from patients with primary biliary cirrhosis (PBC), indicating in vivo activation of C3. Rapid spontaneous C3 cleavage by the classical pathway was observed in vitro in serum and in EDTA plasma reconstituted with Ca++ and Mg++, suggesting the presence of complement-activating substances. On incubation with fresh normal serum, purified polyclonal IgM from patients with PBC induced C1 activation, C4 cleavage, and C3dg formation. No C3 cleavage was observed when PBC-IgM was incubated with a C2-deficient serum. We suggest that the complement activation in vivo in PBC, which occurs predominantly by the classical pathway and is characterized by increased concentrations of C1 activation complexes, decreased C4 concentrations, and hypercatabolism of C3, is attributable to an abnormal IgM population.