Studies of serum complement in the hypocomplementaemic nephritides

Abstract

The sera from forty patients with mesangiocapillary glomerulonephritis (MCGN), fifty-two patients with acute glomerulonephritis (AGN) and twenty-five patients with the nephritis of systemic lupus erythematosus (SLE) were examined for concentrations of C1q, C4, C3, C5, C6, C7, glycine-rich beta glycoprotein (GBG) and properdin, for their ability to generate cobra factor-dependent convertase, and for the presence of C3 splitting activity.

Two types of C3 splitting activity were found. The first, which caused C3 breakdown in normal human serum in the presence of Mg²⁺–EGTA, was in MCGN and in a minority of patients with AGN. The second, which failed to break down C3 in either Mg²⁺–EGTA or EDTA, was found in SLE and AGN. In MCGN and AGN low values of C1q and C4 were found, and there was a significant correlation between the concentrations of these components, suggesting activation of the classical pathway. In SLE much greater reduction in C1q and C4 was observed. Significant reduction in GBG was found in each disease with a significant correlation of GBG with C4 and, in MCGN and SLE, with C3. In AGN and SLE there were significant overall reductions in properdin levels and a good correlation between C3 and properdin, whereas in MCGN, although five of the forty patients had a low properdin there was no correlation between C3 and properdin, and no overall reduction in properdin. These data suggest that complement is activated via the classical and C3b-feedback pathways in MCGN, AGN and SLE, but do not provide evidence for a role for properdin in causing hypocomplementaemia in MCGN.

The two histological variants of MCGN were found to differ in their complement concentrations; patients with intramembranous deposits had a lower C3 concentration and those with subendothelial deposits a lower C4 concentration, suggesting different pathogenetic mechanisms in these two types of MCGN.