Abstract
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 other 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. Therefore, the quantitation of complement breakdown products by simple immunochemical methods provides additional information concerning the involvement of complement in disease and new features for the evaluation of the intensity of immune reactions during immune complex diseases.
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Selected References
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