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The metabolism of C3 and C4 in patients with immune complexes and normal complement levels
J A Charlesworth1, P W Peake, J Golding
1Division of Medicine, Prince Henry Hospital, University of New South Wales, Sydney, Australia.
Insights
Immune complexes accelerate the turnover of complement proteins C3 and C4 in patients with rheumatoid arthritis and infection. This suggests complement activation and increased protein synthesis are key for processing immune complexes.
Area of Science:
- Immunology
- Complement System Biology
Background:
- Patients with rheumatoid arthritis (RA) and infections often exhibit immune complexes but normal complement component levels.
- Understanding complement protein metabolism is crucial for diagnosing and managing these conditions.
Purpose of the Study:
- To investigate the metabolism of complement proteins C3 and C4 in patients with detectable immune complexes.
- To determine if significant ongoing complement activation occurs in these patient groups.
Main Methods:
- Radioisotope labeling (125I-C4, 131I-C3) and intravenous injection in 11 RA patients, 11 infection patients, and 11 controls.
- Analysis of complement protein turnover, production, and extravascular/intravascular distribution.
Main Results:
- Significant hypercatabolism of both C3 and C4 was observed in RA and infection groups compared to controls.
- Normal C4 production was noted, despite C4 null alleles in some RA patients; C3 production was significantly elevated in both groups.
- Increased extravascular/intravascular distribution of C3 and C4 was found in patients with infection.
Conclusions:
- Immune complex formation is linked to accelerated complement protein turnover, independent of tissue damage or serum concentrations.
- Complement activation and enhanced protein synthesis are vital for effective in vivo immune complex processing.
Abstract:
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.