The metabolism of the complement proteins C3 and C4 was studied in patients with active and inactive systemic lupus erythematosus (SLE) using highly purified, functionally active preparations. Nine patients with active and eight with inactive SLE were examined and 11 control subjects. There was a significant difference in the level of double stranded DNA antibodies, immune complexes, and serum C4 between the patients with active and inactive disease. Seven of 16 patients had detectable C4 null alleles and four had low serum concentrations of complement inhibitors. Each subject received approximately 370 kBq [125I]C4 and 93 kBq [131I]C3. Both patient groups showed significant C4 hypercatabolism compared with control subjects, but there was no difference between patients with active and inactive disease. The fractional catabolic rate (FCR) of C4 was comparable in subjects with and without detectable C4 null alleles. C4 production rate was significantly lower in patients with active SLE than in control subjects. There was significant C3 hypercatabolism for both patient groups, but C3 production was normal. An inverse correlation was observed between serum concentration and FCR. There was a highly significant correlation between C4 FCR and C3 FCR for control subjects + patients with inactive disease but not for those with active SLE combined with either controls or the inactive group. We conclude that complement hypercatabolism occurs in SLE irrespective of disease activity and that accelerated turnover does not account completely for the low C4 concentration observed in patients with active disease. This low concentration also results from impaired plasma production, which could reflect a high incidence of C4 null alleles or (inhibitory) factors associated with pathological complement activation, or both. Low C4 production could affect generation of the C3 converting enzyme C4b, 2b and thus influence proceeding complement activation.
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