The in Vivo Metabolism of the Third Component of Complement in Systemic Lupus Erythematosus

The in vivo metabolism of purified C3, the third component of complement, labeled with 125‐iodine (125I‐C3) was studied in 17 normal volunteers and in 24 patients with systemic lupus erythematosus (SLE). The latter had varying degrees of disease severity and differing clinical and serologic manifestations. The study sought correlations of patterns of complement metabolism with clinical and laboratory parameters of disease activity. The data indicate that an increased fractional catabolic rate (FCR) of C3 is characteristic of active SLE because the FCR was increased in 14 of 16 patients with active disease but in only 1 of 8 patients with clinically inactive disease. This relationship is further emphasized by the fact that the FCR was increased in all patients with anti‐DNA antibodies and in all patients judged to have severe disease activity. All patients with normal values for FCR and C3 synthesis rate had clinically inactive disease and no patient judged to have active disease had normal values for both determinations. The synthesis rate of C3 was reduced in a total of 10 patients, but this did not correlate with disease activity, duration of disease, therapy, or certain other laboratory data. Causes of hyposynthesis have not been defined although two clinical settings in which it was found were late stage renal disease with inactive SLE, and severe disease activity with hypercatabolism of C3 and a profound reduction in serum C3 concentration. Hypersynthesis of C3, possibly as a compensatory mechanism, was found in 5 of the 7 patients with the highest FCR, one of whom had a normal level of C3 in spite of hypercatabolism. Such data indicate that various mechanisms determine serum C3 levels. This recognition may allow for more knowledgeable clinical interpretation of serum complement concentrations in SLE.