Enrique H. Vallota

Serum Complement Levels in Infancy: Age Related Changes

Summary: Levels 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.Speculation: Low serum complement levels in neonates may contribute to their increased susceptibility to infections. Correlations between synthetic rates of Clq and IgG is suggested as the mechanism responsible for the correlation in serum levels of these proteins after age 1 yr.

Continuing C3 Breakdown after Bilateral Nephrectomy in Patients with Membrano-Proliferative Glomerulonephritis

Serum levels of complement components and of C3 nephritic factor (C3NeF) were measured serially in two patients with membrano-proliferative glomerulonephritis who were subjected to bilateral nephrectomy and maintained by peritoneal dialysis for 2 wk before renal transplantation. In both patients, low levels of C3 and high levels of preformed alpha 2D, a C3 breakdown product, were present before nephrectomy and remained essentially unchanged during the anephric period. With transplantation, C3 levels rose towards normal and alpha 2D disappeared from the serum. The serum of both patients contained detectable amounts of C3NeF, a factor which has been shown to react with a cofactor found in normal serum to form an enzyme, designated C3 lytic nephritic factor (C3LyNeF), which will cleave C3 to form the breakdown products, beta1A and alpha 2D. The level of C3NeF was high in one patient before nephrectomy, increased somewhat during the anephric period, and fell after transplantation. In the other patient, the C3NeF level was initially lower, remained relatively constant during the anephric period, and was not significantly affected by transplantation. In both patients, levels of C4 and C5 were either normal or elevated over the period of the study and bore no relationship to the C3 level. The following conclusions can be drawn from the data. The high levels of alpha 2D during the anephric period and the disappearance of this protein as C3 levels approach normal at the time of transplantation indicate that the low C3 levels were largely the result of C3 breakdown rather than diminished synthesis. The presence of C3NeF in detectable amounts in both patients suggest that C3LyNeF, formed by the reaction of C3NeF and cofactor, was responsible for the low C3 levels. Finally, the lack of effect of nephrectomy on C3, alpha 2D, and C3NeF levels indicate that the site of C3 breakdown was extrarenal and that C3NeF and cofactor are at least in large part of extrarenal origin.

The C3 nephritic factor andmembranoproliferative nephritis: Correlation of serum levels of the nephritic factor with C3 levels, with therapy, and with progression of the disease+

In the absence of corticosteroid therapy, the serum of all of 12 patients with membranoproliferative nephritis produced C3 breakdown which could be attributed, at least in part, to the C3 nephritic factor (C3NeF). Without therapy an inverse correlation between C3 and C3NeF levels was apparent in serial specimens; with steroid therapy this correlation was lost, and the levels of C3NeF tended to be lower and those of C3 higher. The lack of correlation with therapy is best explained by an effect of corticosteroid in diminishing the availability of cofactor. The data give no clear-cut evidence that the presence of high concentrations of C3NeF in the serum are associated with deterioration of renal function. If C3NeF does cause renal injury, the mechanism appears not to be directly dependent on the serum level of either C3 or C3NeF.