Evidence for In Vivo Breakdown of β1C-Globulin in Hypocomplementemic Glomerulonephritis *

Abstract

Summary. Evidence has been obtained for the presence in vivo of alpha2D-globulin, a breakdown product of serum f10-globulin, in patients with acute and persistent hypocomplementemic glomerulonephritis. The protein has been identified by immunoelectrophoretic analysis, and the amounts present have been determined by direct measurement of specific antigenic determinants present on alpha2D. 831A-Globulin, another breakdown product of Plcglobulin, may also be present in vivo in severely hypocomplementemic patients, but its levels are much lower than those of alpha2D-globulin.Alpha2D-globulin has been identified by immunoelectrophoretic analysis of fresh EDTA plasma from patients with hypocomplementemic nephritis as an arc in the alpha2 region that shows a reaction of identity with the arc representing alpha2D-globulin produced by aged normal serum. 831A-Globulin was not seen in these patterns.Measurement of specific antigenic determinants has been carried out in both fresh EDTA plasma and aged serum. In the fresh plasma, the concentration of D antigen, found on both Plw-and alpha2D-globulins, has been related to that of B antigen, found only on /31c and taken as a measure of the concentration of this protein. In the hypocomplementemic patients, the concentration of D antigen, in comparison to that of B, was greater than in the normal subjects. Similarly, in aged serum, the level of alpha2D was greater than would be expected from the amount of flic that had been broken down in vitro, measured by the concentration of ,81A.Calculations indicated that the in vivo alpha2D level in severely hypocomplementemic patients ranged from 7.5 to 18% of that which would be found in a pool of aged normal serum in which /3ic is completely broken down. The levels tended to be lower in less severely hypocomplementemic patients, and none could be detected in normal plasma.Only small quantities of A and D antigens are detectable in the urine of patients with hypocomplementemic nephritis. The rate of excretion is about equal to that of the normal subject.The study indicates that the low serum levels of fl3c-globulin that may be present over long periods in patients with persistent hypocomplementemic glomerulonephritis can be ascribed, in part, to in vivo breakdown of this pro-

Continuing C3 breakdown after bilateral nephrectomy in patients with membrano-proliferative glomerulonephritis

“…This C3 breakdown product was measured in aged serum and the results expressed in arbitrary units as described previously (8). As noted in that publication, the alpha 2D of aged serum comprises that formed from breakdown of C3 during aging and that which is preformed by in vivo breakdown of C3 and present in the blood at the time it is drawn.…”

“…The hypocomplementemia in other types of nephritis is usually ascribed to in vivo activation of complement by glomerular-bound immune complexes (5)(6)(7)(8). In several types of experimental nephritis in animals, the presence of such complexes in the glomeruli and their role in the production of glomerular inflammation has been well documented (9)(10)(11)(12)(13).…”

“…In support of this are the granular deposits of IgG and Clq which can at times be demonstrated in the glomeruli with labeled antibody and the electron-dense subendothelial deposits demonstrable by electron microscopy (4 (26). Details of the use of this method for measurement of C3 were described previously (8,27). Results are expressed as the 11A globulin content of aged serum.…”

“…In normal serum there is no preformed alpha 2D (8) but it may be relatively abundant in the serum of patients with hypocomplementemic nephritis. To calculate the concentration of circulating preformed alpha 2D, use was made of the fact that when normal serum containing no preformed alpha 2D is allowed to age in vitro, breakdown of C3 causes formation of alpha 2D corresponding to approximately 21 U of D antigen per mg of 81A formed (8). This ratio, desig- nated R in the calculation, is independent of the C3 concentration of the normal serum.…”

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

“…Furthermore, it is known that C3 exhibits several antigens, among them a "native" antigen present only on the native molecule of C3, and an antigen (the main antigen of C3c) present on native C3 as well as on C3b and C3c fragment (17,18). The level of C3 has been measured in synovial fluids by means of either a specific anti-native C3 antiserum or an anti-C3c antiserum to estimate the amount of C3 that has undergone cleavage.…”