Hypercatabolism of the third component of complement in patients with primary biliary cirrhosis

The possibliity that the disturbed immunity associated with primary biliary cirrhosis (PBC) includes abnormal metabolism of the complement system has been investigated by conducting simultaneous studies of the turnover of highly purified, hemolytically active, 125-i-labeled C3 (third component of complement) and 131i-albumin in seven control subjects and nine patients with PBC. Aliquots of each 125i-C3 preparation were injected, together with 131i-albumin, into one or two normal subjects and one to three patients with PBC and plasma and urine radioactivity data were analyzed. In all patients with PBC disappearance of 125i from plasma was much more rapid than in controls. In five of these patients no terminal monexponential decline of 125i occurred. The mean fractional catabolic rate (FCR) of C3 was higher in PBC (4.23 +/- 0.32 [S.E.M.] per cent IV pool per hour) than in controls (2.02 +/- 0.08% IV pool per hour, p less than 0.0005). In contrast, the mean FCR of albumin was similar in PBC (11.4 +/- 1.29 per cent IV pool per day) and controls (11.5 +/- 0.76 per cent IV pool per day), suggesting that the increased FCR of C3 in PBC was not due to a nonspecific process. There was no correlation between values for the FCR of C3 and indices of cholestasis. The mean synthetic rate of C3 was higher in PBC (2.94 +/- 0.48 MG. PER KILOGRAM PER HOUR) THAN IN CONTROls (1.03 +/- 0.11 mg. per kilogram per hour, p less than 0.0025). In five patients relatively more C3 was extravascular than in controls. The results are consistent with PBC being associated with chronic activation of the complement system and increased tissue attachement of C3, phenomena which could be related to a process of pathogenic significance in this disease.