Complement breakdown products in plasma from patients with systemic lupus erythematosus and patients with membranoproliferative or other glomerulonephritis.

Abstract

A B S T R A C T A dynamic estimation of the involvement of the complement system in various diseases was obtained by the direct quantitation of breakdown products of C3 and of properdin factor B. The methods used were based, first, on the separation of native and fragmented molecules according to their molecular size through a precipitation with polyethylene glycol and, secondly, on an immunochemical quantitation, using specific antisera for the major antigens of C3 and factor B. The sensitivity and the specificity of these methods were demonstrated by activation of complement in vitro with generation of C3 and factor B fragments.A clinical investigation was carried out in 41 patients with systemic lupus erythematosus (SLE), 31 with membranoproliferative glomerulonephritis (MPGN), 26 with other types of glomerulonephritis, and 6 with severe alcoholic cirrhosis of the liver. The following observations were made: (a) an elevated plasma level of C3d fragment of C3 was found in 68% of SLE patients, in 87% of MPGN patients, in 62% of patients with other hypocomplementemic nephritis, and in 15% of those with normocomplementemic nephritis, but in only 33% of patients with liver cirrhosis and very low levels of C3; (b) a significant difference was observed between the levels of C3 obtained with either anti-"native" C3 or anti-C3c sera for immunochemical quantitation, in patients with SLE or MPGN, indicating the presence of "altered" or fragmented C3 in plasma; (c) an elevated plasma level of Ba fragment of properdin factor B was found in 46% of SLE patients, in 67% of MPGN patients, in 50% of patients with otherThis work was presented in part at the European Complement Workshop, Heidelberg, May 1974.Dr. Lambert's address is: Centre de Transfusion, HopitalCantonal, 1211 Geneva 4, Switzerland. Received for publication 9 December 1974 and in revised form 18 March 1975. hypocomplementemic nephritis, and in 9% of patients with normocomplementemic nephritis, while the level of properdin factor B was only slightly decreased in these diseases; (d) in SLE and MPGN there was an inverse correlation between the levels of C3d and Ba and the level of C3 in plasma. The level of these fragments was directly correlated with the clinical manifestations of SLE; (e) some patients with a normal C3 level exhibited an elevated plasma concentration of C3 and factor B fragments, suggesting the coexistence of an increased synthesis with a hypercatabolism of complement components.

Correlation between levels of breakdown products of C3, C4, and properdin factor b in synovial fluids from patients with rheumatoid arthritis

“…It has been shown that in vitro generation of breakdown products preceding the analysis hardly ever occurs under the conditions used for storage and handling of test samples (15). All measurements were made in duplicate and were repeated if the variation exceeded 10%.…”

“…Recently methods have been developed to directly quantitate C3d, C4d, and Ba fragments resulting from the breakdown of C3, C4, and factor B respectively R A + __ A (15,16). These techniques have been applied to the investigation of patients with systemic lupus erythematosus and various types of glomerulonephritis (15). I n the present investigation the hypercatabolism of C3, C4, and factor B was investigated in synovial fluids from patients with RA and other articular diseases through quantitation of the corresponding breakdown products.…”

Cleavage of C3 by Neutral Proteases from Granulocytes in Pleural Empyema

“…The results were expressed as a percentage of the levels in a pool of normal human plasma. C3d levels were quantitated in a two-step procedure [23]. In the first step, native C3 and the high-molecular-weight fragments C3b and C3c were precipitated with polyethyleneglycol.…”

Sensitivity and specificity of plasma and urine complement split products as indicators of lupus disease activity

“…Depression of serum C3 and C 4 levels may not always accurately reflect complement activation. C3 acts as a n acute-phase reactant, and a n increase in production with inflammation may mask its consumption (11,12). Another problem with measurement of complement occurs in lupus patients with genetically determined complement deficiencies (13,14).…”