SummaryLevels of eight complement components and two control proteins, were determined on cord serum from normal full term neonates and serum from healthy infants aged 1 and 6 months. For all proteins, the levels were below the adult normal at birth and rose toward the adult range by age 6 months. In a second group of 271 patients, ages 1-36 months, serum Clq and properdin levels were measured. For both proteins, the mean values in early infancy were more than two SD below the adult range and did not reach the adult range until 18-21 months of age. The Clq concentration was more variable than that for any other component studied. In infants from 11 months-3 yr of age, Clq levels correlated with serum IgG levels, but properdin levels did not.

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.

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-

The control of the amplification C3 convertase, C3b,Bb, of the serum complement system has been found to be defective in five members of a family spanning three generations. One of the five has membranoproliferative glomerulonephritis (MPGN) type III and another has mild idiopathic rapidly progressive glomerulonephritis. The defect is manifested by low serum concentrations of C3 and usually factor B with normal levels of the proteins which control the convertase, H and I. C3 nephritic factor (C3NeF) was not demonstrable. Enhanced C3 conversion was produced by the incubation of their serum at 37 degrees C for 30 min. This conversion was further accelerated by incubation after increasing the serum magnesium concentration by increments ranging from 0.25 to 1.9 mM. Incremental additions of H to serum depleted of H indicated that the amplification convertase of affected family members required more H for its inhibition than did that of normal subjects. This requirement was reduced by the addition of purified normal C3 but not by the addition of purified C3 of the propositus. It is postulated that affected family members are heterozygous for a gene producing an abnormal C3 which, as a constituent of the amplification convertase, C3b,Bb, confers resistance to H. Investigation of this apparently nephritogenic defect may provide insight into the pathogenesis of these glomerulonephritides.