Deficient Alternative Complement Pathway Activity in Newborn Sera

Abstract

Summary: Neonatal susceptibility to overwhelming bacterial infection is commonly attributed to a relative deficiency in serum opsonic activity. However, few studies have compared the functional capacity of the classical complement pathway with that of the alternative complement pathway in the neonate. The opsonic activity of nine maternal infant serum pairs were studied by determining percent uptake of radiolabeled Escherichia coli Seven mother-infant paired sera were studied using E. coli strains known to be opsonized via the alternative complement pathway: the mean percent uptake of E. coli opsonized in neonatal sera was 16.8%; of those opsonized in maternal sera, 54%; and of those opsonized in control sera, 45% (P < 0.005). Two E. coli strains requiring the classical complement pathway for opsonization were phagocytized equally well in maternal and infant sera of seven mother-infant pairs. Determination of anti-O hemagglutination inhibition (HI) antibody titers in six maternal sera for one classical complement pathway activating and one alternative complement pathway strain showed no correlation between percent phagocytosis and HI antibody titer. These data would suggest that serum levels of classical pathway components are probably adequate for opsonization of E. coli via the classical pathway, but that low alternative complement pathway activity in neonatal sera may contribute to the newborn's increased susceptibility to bacterial sepsis. Speculation: There is good evidence that both humoral and cellular deficiencies exist in the inflammatory response of the newborn. The pathogenesis of neonatal E. coli sepsis and meningitis may involve a critical balance between the presence of these immunologic deficiencies and the particular opsonic requirements of the invading organisms. In the adult host, many strains of E. coli are well opsonized by either specific antibody or by activation of the alternative complement pathway. In the neonate, in the absence of transplacentally derived specific antibody, efficient opsonization of these same organisms cannot be accomplished due to low levels of alternative complement pathway activity. Thus, treatment rationale in E. coli sepsis and meningitis may include supplementation with either or both specific antibody and a source of complement activity.