Activity of the alternative pathway of complementin the newborn infant

Adamkin, David H.; Stitzel, Ann E.; Urmson, Joan; Farnett, Mary Lou; Post, Ernest M.; Spitzer, Robert J.

doi:10.1016/s0022-3476(78)80895-6

Cited by 58 publications

(16 citation statements)

References 19 publications

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“…One purpose of this alternative amplification loop is to increase the amount of activated complement factors in the final common pathway and thus increase the total activity of the complement system (24,25). Neonates may have a deficient upregulation of the alternative pathway because of low levels of alternative pathway factors (15,34). A lower activity of the alternative amplification loop may also explain why we observed lower levels of activation products of the final common pathway in cord blood.…”

Section: Discussionmentioning

confidence: 80%

Staphylococcus epidermidis biofilms induce lower complement activation in neonates as compared with adults

et al. 2012

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Background: Staphylococcus epidermidis (se) is an important cause of late-onset sepsis in neonates. se frequently produces a polysaccharide intercellular adhesin (PIa) biofilm, important in the pathogenesis of these infections. Little is known about how the neonatal innate immune system reacts to se biofilm-associated infections. Our hypothesis was that se biofilms induce a lower complement activation in neonates as compared with adults. Methods: cord blood from term infants (n = 15) and blood from adults (n = 6) were studied in an ex vivo whole-blood sepsis model. a PIa biofilm-producing strain (se1457) and its isogenic mutant (M10), producing a non-PIa biofilm, were used. results: Both se biofilms induced stronger complement activation in adult than in cord blood (P ≤ 0.033). We found lower levels of antibodies toward both PIa (P = 0.002) and the whole bacterium (P = 0.001) in cord vs. adult blood. By contrast, the interleukin-8 (IL-8) and IL-6 secretion were higher in cord than in adult blood (P ≤ 0.002). The PIa biofilm induced stronger complement activation than the non-PIa biofilm. conclusion: We conclude that the neonatal complement system exhibits a maturational deficiency. This may reduce the ability of neonates to combat biofilm-associated se infections. Staphylococcus epidermidis (SE) is the most prevalent pathogen causing late-onset sepsis in neonates (1). These infections are seldom lethal, but they cause significant morbidity, especially in preterm infants (1,2). SE infections are often associated with biofilm production on the surface of foreignbody implants (3,4). Biofilms are adherent multicellular bacterial aggregates embedded in a self-produced extracellular matrix. The best-described matrix compound in SE biofilms is a β-(1,6)-linked N-acetylglucosamine named polysaccharide intercellular adhesin (PIA) (5,6).SE and SE biofilms interfere with the host immune response at different levels. PIA biofilms inhibit the action of antimicrobial peptides (7), decrease neonatal inflammatory response (8), and decrease phagocytosis and degranulation by neutrophils (7). Biofilms may "decoy" antibodies and complement on the bacterial surface and thereby decrease opsonization and phagocytosis (9-11). The ability of biofilm-producing bacteria to avoid immune clearance and the general immaturity of the neonatal immune system (12) are postulated to increase the risk of neonatal SE sepsis (13). As compared with adults, neonates have a lower quantitative and qualitative complement activation (14,15), reduced upregulation of cellular response (12), and an immature cytokine response pattern (16)(17)(18)(19). Preterm infants demonstrate a markedly reduced capacity to upregulate oxidative burst in leukocytes in response to SE (20). However, some authors have reported that SE may induce a similar proinflammatory cytokine response in neonates and adults (19,21), indicating a differential maturation of various parts of the neonatal innate immune system. Differences in maturation have also been described when challenging t...

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Section: Discussionmentioning

confidence: 80%

Staphylococcus epidermidis biofilms induce lower complement activation in neonates as compared with adults

et al. 2012

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“…In the few reports also including studies of complement in low birth weight infants, classical as well as alternative complement activity have generally been found to be lower in low birth weight than in normal term infants (1,6,8,14,16). But it is not clear from these studies whether the defect of complement activity in low birth weight infants is the result of premature birth (6,8) or of intrauterine growth retardation (1,14,16). The purposes of the present study were to compare complement activity of both pathways in AGA and SGA low birth weight newborns, and to determine the influence of birth weight and gestational age on complement development in such infants.…”

Section: Discussionmentioning

confidence: 97%

“…Complement factors increase gradually during gestation and intrauterine growth retardation does not affect complement development. 1…”

Section: Discussionmentioning

confidence: 99%

“…Complement activity is lower in low birth weight infants than in term infants; however, the relationship of gestational age and/ or birth weight to the level of complement activity is still controversial (1,6,8,14,16). The purpose of the present study was to investigate the effects of birth weight and gestational age on complement development (CH50 and kinetics of both CP and AP, C3, and Factor B levels) in low birth weight infants divided into appropriate and small for gestational age groups.…”

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confidence: 99%

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Activity of Classical and Alternative Pathways of Complement in Preterm and Small for Gestational Age Infants

et al. 1984

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SummaryComplement activity was compared in 50 low birth weight infants divided into appropriate and small for gestational age groups; the influence of birth weight and gestational age on complement development was also investigated. CHW and kinetics (tHso) of both classical and alternative pathway activity of complement, C3, and Factor B levels were significantly higher in small for gestational age infants (classical pathway CHs, 630 HU/ml f 184 SD, C P tHs, 77 min + 47; aternative pathway CHS0, 44.8 HU/ml & 11.3; AP tHso, 56 min f 43; C3, 73.98 mg/dl f 12.68; and Factor B, 13.17 mg/dl 2 3.67) than in weight-matched appropriate for gestational age infants (CP CHW, 523 HU/ml 2 152; C P tH9, 105 min + 49; AP CHW, 38.8 HU/ml f 13; AP tHW, 90 min 2 53; C3, 58.14 mg/dl f 9.43; and Factor B, 9.32 mg/dl+ 1.73). Complement values were lower in low birth weight infants than in adult controls ( P < 0.001 in all cases). All complement parameters were mainly correlated with gestational age; CHso values of the classical and alternative pathways were also highly correlated with each other

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“…The main reason for these discrepancies lies in the use of different assays, different types of particles, particle size, and different serum concentrations. Concentrations of complement components important for the opsonization of various microorganisms in newborns were found to be relatively low compared with the levels in adults; however, normal and even elevated levels of complement proteins have also been reported (18)(19)(20)(21)(22)(23)(24)(25)(26)(27).…”

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confidence: 99%

Opsonic Activity of Cord Blood Sera against Various Species of Microorganism

et al. 1985

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ABSTRACT. The results of the present study on the opsonic activity of cord blood serum against various microorganisms (Staphylococcus aureus, Escherichia coli, and group B streptococci) show that the activity of cord blood serum in promoting IgG-mediated ingestion is equal to that of sera of healthy adults. This implies that IgG concentrations, as assessed by immunochemical methods, in cord blood and adult sera represent functionally similar IgG activities. Ingestion of microorganisms involving complement-dependent opsonization was found to be of the same level for cord blood and adult sera, when the opsonization occurred via the classical pathway of complement activation. However, due to decreased concentrations of factors B, P, and D in cord blood serum, optimal opsonization of microorganisms requiring the alternative pathway of complement was impaired. Taken together, these results indicate that an opsonic defect of cord blood serum affects mainly microorganisms requiring opsonization via the alternative pathway of complement. (Pediatr Res 19: [433][434][435][436]1985)

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Activity of the alternative pathway of complementin the newborn infant

Cited by 58 publications

References 19 publications

Staphylococcus epidermidis biofilms induce lower complement activation in neonates as compared with adults

Staphylococcus epidermidis biofilms induce lower complement activation in neonates as compared with adults

Activity of Classical and Alternative Pathways of Complement in Preterm and Small for Gestational Age Infants

Opsonic Activity of Cord Blood Sera against Various Species of Microorganism

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