Accelerated nonproteolytic cleavage of C3 in plasma from patients with primary biliary cirrhosis.

Complement 3 (C3) with decreased net charge and altered immunoreactivity was detected by crossed immunoelectrophoresis when EDTA plasma from patients with primary biliary cirrhosis was incubated in vitro after reconstitution with Ca++ and Mg++. The alpha and beta chains of this C3 were intact. C3 with decreased net charge was not detected in patients' fresh plasma. Similar C3 alterations were obtained after reaction between native C3 in serum from healthy persons or purified C3 nucleophiles that induce cleavage of the single thioester bond in the alpha chain of C3. This C3 alteration was unchanged when the reaction occurred in the presence of protease inhibitors. The electrophoretically slow C3 fraction was labile in serum on further proteolytic cleavage of C3. It is suggested that accelerated nonproteolytic C3 cleavage in patients with primary biliary cirrhosis facilitates subsequent binding of C3 to C3b receptors and targets of complement attack.