The serums of patients with hypocomplementemic glomerulonephritis contain a substance that combines with a normal serum cofactor in the presence of magnesium ion to specifically cleave the third component of complement. This lysis of C'3 is 80 to 90 percent complete in 20 minutes at 37 degrees C and pH 7. Neither the nephritic factor nor its cofactor is identifiable with the complement system.

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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-

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All immune origin of glomerulonephritis, with complement playing a major role, was first suspected 50 yr ago when it was found that serum complement levels in nephritis were often low. Only recently however, with the identification of individual components, have details of the complement reaction become susceptible to investigation. It is already apparent that there are differences in the way in which complement is involved in nephritis. For example, serum levels of individual components have been shown to be variably reduced depending upon the type of nephritis (1-3). Furthermore, deposition of C3 in the glomeruli occurs in many cases in which C3 and total complement levels have remained normal during the course of the disease (4-6). In other types of nephritis, however, the configuration of C3 deposition correlates well with the supposed target of the immune reaction (4, 5).The participation of complement in producing the type of nephritis designated hypocomplementemic persistent or membranoproliferative is of special interest. In this disease CHs0 and C3 may remain at very low levels over long periods (6, 7) and C3 is usually found in the glomerular capillary walls by immunofluorescent techniques, often without the presence of identifiable IgG. 1 The persistently reduced serum levels of C3 have been explained by some as the result of diminished synthesis of C3 (8) and ascribed by others to an ongoing complement reaction in the glomeruli in which C3 is continuously being broken down (9). Recent observations suggest that a site of complement breakdown may be circulating plasma. Inactivators of guinea pig (10) and human (11) complement have been found in the serum of patients with acute, chronic hypocomplementemic, and lupus nephritis, and in a previous communication from this ]nboratory, Spitzer et al. (12) reported the presence of a factor in the