Deficiencies in Opsonic Defense to Pneumococci in the Human Newborn Despite Adequate Levels of Complement and Specific IgG Antibodies

Abstract

ABSTRACT. We studied the major determinants of opSystemic infection due to Streptococcus pneumoniae is a serisonophagocytosis against Streptococcus pneumoniae sero-ous disease in the neonatal period. In many infants the infection types 14 and 19 in paired cord/maternal sera from 27 runs a fulminant course with a fatal outcome in 50%. The healthy term and 24 preterm infants in an attempt to gain incidence of neonatal pneumococcal septicemia, however, is low. more insight in the susceptibility of newborns to pneumo-S. pneumoniae causes approximately 5% of all neonatal septicoccal infection. For both pneumococcal serotypes studied, cemia~ (1). Results of epidemiologic studies suggest that the opsonic activity in neonatal sera varied greatly, but was majority of infants with neonatal pneumococcal septicemia acmoderately to profoundly deficient when compared to quire the microorganisms either by the ascending route or during pahed maternal sera, both in preterm (34.5 and 34.9% of passage through the birth canal. The rarity of neonatal pneuthe activity in maternal serum, for serotypes 14 and 19, mococcal disease is probably due to the low incidence of camage respectively, p < 0.001 for both) and in term serum (43.5 of pneumococci in the genital tract (2-4). and 52.7% of the activity in maternal serum, for serotypesTo gain better insight in the apparent susceptibility of the 14 and 19, respectively, p < 0.001 for both). The opsonic newborn to pneumococcal septicemia, we determined the efideficiency in preterm sera could be ascribed to a diminished ciency of opsonophagocytosis of pneumococci in paired cord/ level of the major opsonins for pneumococci, i.e. comple-maternal sera of healthy term and premature neonates. This ment factor C3 deposited on the bacterial surface (69.5 process is one of the major host-defense mechanisms against and 66.2% of C3 deposition in maternal serum on serotypes such bacteria in man.14 and 19, respectively, p < 0.01 for both) and specific anticapsular IgG antibodies (48.5 and 14.1 % of maternal MATERIALS AND METHODS levels for serotypes 14 and 19, respectively, p < 0.001 for both). However, the opsonic defect in serum from term Sera. Serum was collected from the umbilical cord directly infants could not be explained in a similar way, because postnatally or by venipuncture within 48 h of birth from 27 C3 deposition and specific anticapsular IgG levels were healthy term neonates (mean gestational age 40 wk, range 37-equal to the values found in the paired maternal sera. 42 wk; mean birth wt 3447 g, range 2750-4250 g), 20 preterm Therefore, we conclude that the opsonic defect in newborn neonates (mean gestational age 33 wk, range 28-36 wk; mean serum for pneumococci cannot be solely explained by a birth wt 2064 g, range 1200-3400 g), and four immature neonates deficiency in the major opsonins for these bacteria. A (mean gestational age 26 wk, range 25-26 wk; mean birth wt dysfunction in these opsonins seems to be a more likely 1022 g, range 755-1330 g). These newborns were hospitalized in expl...

The Role of Mannose-Binding Lectin in Susceptibility to Infection in Preterm Neonates

“…Indeed premature neonates of less than 32 wk of gestation have fetal IgG concentrations of less than 50% of maternal levels (6,7). Many elements of the acquired immune system are also either low or function sub-optimally (8,9). It is in these circumstances, that the innate immune system may be particularly important in providing protection against infection.…”

Does IVIg administration yield improved immune function in very premature neonates?

“…Geelen et al 32 PMN FcgRIII (CD16) surface expression that persisted over at least the first 3 weeks of post-natal life. In contrast, PMN surface expression of FcgRI (CD64) is significantly elevated in very premature neonates at birth versus birth levels in term neonates and at baseline in adults, but equilibrates to levels seen in growing term neonates within the first month of life.…”

“…31 The effect is largely dependent on the presence and functional activity of complement. 32 Furthermore, opsonization has little effect in the absence of competent cellular function that is required to engulf and kill the pathogens after effective opsonization. Preterm (28-34 weeks GA) neonates exhibit decreased PMN opsonic capacity, phagocytosis and respiratory burst compared with term neonates and adults, 15 and this may be worse in very premature neonates.…”

“…42 Complement deposition on S. pneumoniae was equivalent in term and adult serum, but significantly lower in serum from preterm neonates (28-33 weeks). 32 A single study used pooled serum from two healthy preterm neonates with birth weights <850 g and found that addition of IVIg increased C3 deposition on CoNS. 43 Future studies to provide greater resolution of the functional deficits in complement activation and to show how these deficiencies respond to IVIg in premature neonates will be essential to understand the mechanisms behind the benefits or lack of benefits of IVIg therapy.…”

“…16 Studies in preterm neonates have shown the importance of complement activation for effective opsonophagocytosis. 32,[36][37][38] PMNs from premature neonates (mean age at birth, 31 weeks) showed that FcgRIII (CD16) has a major role in opsonophagocytosis of coagulase-negative Staphylococcus (CoNS), the predominant pathogen associated with late-onset sepsis in the very premature neonate, 39 but again complement is required. 36 As discussed previously, FcgRIII (CD16) expression on very premature neonate PMNs is profoundly decreased at birth, remains low over the first post-natal weeks and is decreased further with clinical stress.…”