Impaired Chemotaxigenesis by Type III Group B Streptococci in Neonatal Sera: Relationship to Diminished Concentration of Specific Anticapsular Antibody and Abnormalities of Serum Complement

Abstract

Summarynates and other individuals with disorders characterized bv a high A chemotaxigenesis (CTG) assay employing adult or neonatal sera, type I11 group B streptococci (GBS) and polymorphonuclear leukocytes (PMNs) was designed to evaluate the role of PMN mobilization in the pathogenesis of type 111 GBS infection in neonates. Generation of C5a in healthy adult sera with moderatehigh (3-40 pg/ml) or low (52 pg/ml) levels of specific anticapsular antibody was confirmed by PMN aggregometry and by the neutralization of CTG by goat anti-human C5. CTG was significantly ( P < 0.001) greater in high as compared to low specific antibodycontaining adult sera; stepwise increases in CTG occurred when specific IgG was added to untreated, but not heat-inactivated, hypogammaglobulinemic serum. Immunospecificity of CTG was shown by a failure of type 111 GBS to generate C5a in heterologous (type Ia) high antibody sera. Mean CTG values in three high and 16 low antibody-containing sera from healthy term neonates were 24% and 62% of high ( P < 0.001) and low (P < 0.01) antibody adult sera, respectively. The addition of both complement and specific IgG to low antibody-containing neonatal sera was required to enhance their CTG activity to high antibody adult values. CTG by type I11 GBS in neonatal sera-neonatal PMN mixtures was only 25% (high antibody sera) and 14% (low antibody sera) of values for paired maternal sera mixtures reacted with adult PMNs ( P < 0.001). These studies demonstrate that CTG by type I11 GBS in neonatal sera is markedly diminished and that low concentrations of specific anticapsular antibody and abnormalities of complement function contribute to impaired PMN mobilization in human neonates. AbbreviationsAb, antibody ACP, alternative complement pathway C4D, C4 deficiency CH50, hemolytic complement activity CL, chemoluminescence CTG, chemotaxigenesis DPBS, Dulbecco's Phosphate Buffered Saline GBS, group B streptococci GPS, guinea pig sera PMN, polymorphonuclear leukocyte THB, Todd-Hewett broth ZAP, zymosan-activated plasma Among inflammatory functions, the localized recruitment of phagocytic cells to foci of microbial invasion represents a critical and first line host defense mechanism (5, 32, 49). Impaired leukocyte tissue mobilization has been demonstrated in human neo-, U risk for the development of severe pyogenic infections (5,19,37). Previous investigations in human neonates have demonstrated abnormalities in both the humoral and cellular contributions to leukocyte motility in vitro (5,22,25,27,3 1,33,36,46), but specific serum requirements for generation of chemotactic factors (chemotaxigenesis) by GBS have not been determined. The experiments described in this report were designed to study the chemotactic properties of type 111 GBS and to define chemotaxigenic requirements in human sera for this serotype. Methods were developed to evaluate selectively the functional importance of serum antibody (IgG) specific for native 111 capsular polysaccharide and complement in the generation of C5a by GBS in sera fro...

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