Decreased synthesis of the third component of complement (C3) in hypocomplementemic systemic lupus erythematosus

Abstract

Metabolism of the third component of complement (C3) was evaluated in eight normal subjects and nine patients with systemic lupus erythematosus (SLE). Six of the nine patients with SLE were hypocomplementemic; four of these had active renal disease. In the eight normals, the half-life survival (T 1/2) was 49–66 hr, the catabolic rate (Km) was 1·8 to 3·5% of plasma pool/hr, and the synthetic rate (Ks) 0·89–2·0 mg/kg/hr. Two SLE patients with normal C3 had a normal T 1/2, Km and Ks; one with increased C3 had a shortened T 1/2 and a high Km and Ks. Three patients with untreated SLE and depressed C3 had T 1/2 of 21 hr, 37 hr, and 69 hr, Km of 5·3%, 3·5% and 1·6% with Ks of 0·48, 0·95 and 0·23 mg/kg/hr, respectively. Three other patients with low C3 levels taking corticosteroids had normal Km but depressed Ks. Three patients were restudied after prednisone therapy. All had an increased C3 and Ks, two had an increase in T 1/2 and a decrease in Km, while one did not change T 1/2 or Km. In summary, five of six SLE patients with low C3 had a depressed Ks. The lowest value of C3 was generally associated with the lowest Ks. Depressed Ks occurred in patients with or without renal disease. These results indicate that static measurements of C3 do not quantify the degree of C3 utilization. The major determinant of the low C3 observed in this study of SLE was decreased synthesis of C3.