Deficient Classical Complement Pathway Activity in Newborn Sera

Abstract

SummaryThe bactericidal activity of 20 maternal-neonatal paired sera was assessed employing a clinical type Ia, group B streptococcal isolate, strain 515, known to be opsonized by the classical complement pathway in a non-antibody dependent fashion. Twelve neonatal sera had efticient bactericidal activity for this isolate (mean 96%, range 91-99%) whereas eight had significantly lower bactericidal indices (mean 29%, range 0-54%) ( p < 0.001). The mean bactericidal index for 20 maternal sera (88%) did not differ from that of 20 adult control sera (91%). Bactericidal activity was not influenced by the concentration of antibody to the capsular polysaccharide antigen of type Ia, group B Streptococcus present in these sera. When the classical pathway of selected neonatal sera with high or low bactericidal activity was inactivated by MgEGTA chelation of C1, bacterial growth was observed uniformly when concentrations of specific antibody were low. The bactericidal index of neonatal sera correlated significantly with the total hemolytic complement titer ( r = 0.611, P < 0.01). The mean levels of each complement component or control protein assessed by radial immunodiffusion (Clq, C4, C3, B, H, and I) were lower in neonatal sera with low than in those with efficient bactericidal activity, and levels of Clq and H were depressed significantly (P < 0.025 and <0.001, respectively). Hemolytic titers of C4 but not C1 or C2 were also significantly lower for low than for selected high-killing neonatal sera (P < 0.05). Bactericidal activity in neonatal serum with a bactericidal index of zero was restored in a dose-dependent fashion by the addition of fresh frozen plasma. Abbreviations BI, bactericidal index CHSO, whole complement activity EGTA, ethyleneglycoltetracetate FFP, fresh frozen plasma GVB, Veronal-buffered saline containing 0.1% gelatin GVB++, GVB containing 0.5 mM Mg++ and 0.15 mM Ca++ MgEGTA, GVB supplemented to 4 mM Mg++ and 16 mM EGTA adjusted to pH 7.5 OD, optical density THB, Todd-Hewitt brothThe levels of individual classical complement pathway components in neonatal sera have been shown to be significantly lower than those in adults (1,6-7, 11-12, 19). Davis et al. (6) have shown that by the age of 6 months the mean concentrations of C2 and C4 have increased to levels not significantly different from those of adults, but Clq and C3 concentrations remain low. Few studies have compared the functional capacity of the classical pathway for a pathogen common in the neonate with the degree of depression of individual classical pathway components. We have shown previously that bactericidal activity in adult sera for a variety of clinical isolates of type Ia, group B streptococci was mediated by the classical complement pathway in a non-antibody dependent fashion (2). Both adult sera deficient in specific antibody and agammaglobulinemic serum, which had no detectable antibody to the capsular polysaccharide antigen of type la, group B Streptococcus supported efficient bactericidal activity for each of 18 clinical type Ia...

Biochemical Abnormalities of the Third Component of Complement in Neonates

“…In several studies, decreases in complement-mediated opsonization or bacterial killing in neonatal serum have correlated with reduced serum levels of various complement components including factor B (10,27), C3 (28), Clq, C4, and factor H (12). However, in many cases, defects in neonatal complement function have been reported despite relatively normal serum concentrations of C3 (10,12). These latter reports give rise to the hypothesis that the function of C3 may be aberrant in the neonate, even though the C3 concentration is essentially normal.…”

“…Previous studies of complement function in neonates have demonstrated impairments in both the classical and the alternative pathways (9)(10)(11)(12)(13). In several studies, decreases in complement-mediated opsonization or bacterial killing in neonatal serum have correlated with reduced serum levels of various complement components including factor B (10,27), C3 (28), Clq, C4, and factor H (12).…”

“…Some have found lower levels in the premature infant in comparison to the term newborn (8,(10)(11)(12). We used a sensitive ELISA assay for measurement of C3 concentrations and calibrated it with known concentrations of purified human C3 as an internal Fig.…”

“…In addition, function of the newborn's complement system is also impaired and may increase the risk of infection (9)(10)(11)(12)(13). For example, Cairo et al (14) have recently shown that a low CH50, a measure of the hemolytic activity of complement, is the most significant determinant of mortality in septic newborns, regardless of gestational age.…”

“…Previous studies have demonstrated quantitative deficiencies in C3 and other complement proteins in the neonate (8)(9)(10)(11)(12). In addition, function of the newborn's complement system is also impaired and may increase the risk of infection (9)(10)(11)(12)(13).…”