Properdin and C3 Proactivator: Alternate Pathway Components in Human Glomerulonephritis

Abstract

A B S T R A C T Serological and immunopathological studies of human glomerulonephritis have suggested that alternate pathways of activation of the third component of complement may be important in some forms of glomerulonephritis. We have investigated the role of two alternate pathway proteins, properdin and C3 proactivator, in 22 patients with chronic membranoproliferative glomerulonephritis, 21 patients with systemic lupus erythematosus, 20 patients with acute poststreptococcal glomerulonephritis, and 19 patients with other forms of renal disease. C3 (measured at PA), properdin, and C3 proactivator were assayed by single radial immunodiffusion.In sera with low PA (< 2 SD), mean properdin was most significantly decreased in patients with acute poststreptococcal glomerulonephritis but was also significantly decreased in chronic membranoproliferative glomerulonephritis and in untreated systemic lupus erythematosus. Properdin levels in other renal disease, acute glomerulonephritis, and chronic membranoproliferative glomerulonephritis with normal fiA levels were not significantly different from normal. A positive correlation between PA and properdin levels in individual sera was present in all diseases except systemic lupus erythematosus.Serum C3 proactivator was markedly decreased in active systemic lupus erythematosus and there was a positive correlation between fi1A and C3 proactivator levels in systemic lupus erythematosus and other renal diseases but not acute poststreptococcal glomerulonephritis.Properdin in fresh sera from four patients with systemic lupus erythematosus and five with chronic membranoproliferative glomerulonephritis showed increased migration toward the cathode on immunoelectrophoresis, suggesting in vivo change of the properdin molecule.

Homozygous C2 deficiency with fulminant lupus erythematosus. severe nephritis via the alternative complement pathway

“…Decreased levels of serum properdin factor B and/or deposition of properdin in skin and kidney have been observed in certain patients with SLE (46)(47)(48)(49). The present study would suggest that under appropriate conditions involvement of the properdin system may further result in severe and even fatal disease, although clearly this represents an unusual experience.…”

Human C4-binding protein. Association with immune complexes in vitro and in vivo.

“…In a limited survey of biopsies of patients with acute poststreptococcal glomerulonephritis, C3 was uniformly present, while IgG, C4, and C4-bp were absent in some. This point requires further observation in more patients, but suggests that, as in other biopsies from patients with poststreptococcal glomerulonephritis in which properdin was found, the alternative pathway of complement activation may be operative (15).…”

Metabolic Studies of the Third Component of Complement and the Glycine-Rich Beta Glycoprotein in Patients with Hypocomplementemia

“…The capacity of labeled GBG to produce a cobra-factor-dependent C3-convertase was then tested by incubation with purified cobra factor (CoF) and R (GBG). The activity of the C3-convertase generated was measured by the lysis of guinea pig erythrocytes in the presence of human EDTA serum (18 of the study and the doses of radioactivity (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)uCi) were approved by the Medical Research Council. Thyroidal uptake of iodide was blocked by oral potassium iodide, 180 mg daily for 3 days, before radioactivity was administered.…”