The metabolism of C3 and C4 in patients with immune complexes and normal complement levels.

The metabolism of the complement proteins, C3 and C4 was examined in two groups of patients with a high incidence of detectable immune complexes but normal levels of complement components. The specific aim was to ascertain whether significant ongoing complement activation occurred in these patients. Eleven patients with rheumatoid arthritis (RA), 11 with infection and 11 control subjects were studied. Each received approximately 10 microCi 125l.C4 and 2.5 microCi 131l.C3 by intravenous injection. Analysis of turnover data showed that there was significant hypercatabolism of both C3 and C4 in the two study groups compared to controls. Plasma production of C4 was normal for both groups (despite the presence of C4 null alleles in six out of 11 of the RA group), while C3 production was significantly elevated in both RA and infection (p less than 0.01 and p less than 0.001 respectively). Patients with infection showed a significant increase in extravascular/intravascular distribution of both proteins. The data show that immune complex formation is associated with accelerated turnover of complement proteins, irrespective of co-existing tissue damage or changes in the serum concentration of complement components. The findings suggest that both activation of complement and maintenance or enhancement of protein synthesis are important for the efficient processing of immune complexes in vivo.