Plasma concentrations of C4b‐binding protein and vitamin K‐dependent protein S in term and preterm infants: low levels of protein S‐C4b‐binding protein complexes

Abstract

We have determined the plasma concentrations of protein S and C4BP in 25 term and 26 preterm infants by radioimmunoassay. Both the total concentration and the concentration of free protein S were quantified. The concentration of C4BP was very low in preterm infants (mean 6% of the adult level). In term infants, the level had increased to a mean of 18%. Total protein S was decreased both in preterm and term infants, 4.0 mg/l and 6.8 mg/l respectively, as compared to the mean adult concentration, 20.6 mg/l. In preterm infant plasma, free protein S was the predominant (85%) form, probably due to the very low C4BP level. In plasma from term infants, free protein S represented 68% of the total protein S, the corresponding value in adult controls being 37%. The plasma concentration of free protein S in preterm and term infants was 3.3 mg/l and 4.6 mg/l, respectively (mean adult value 7.6 mg/l). These results demonstrate that, while the total protein S concentration in preterm and term infants was very low in comparison to the adult level, the difference in the concentration of the anticoagulant, active, free form of protein S between infants and adults was less pronounced.

Off to a slow start: Under-development of the complement system in term newborns is more substantial following premature birth

“…However Sthoeger et al (1989) reported that term neonatal C4BP levels had increased to 50% adult levels by 1 week after birth and attained adult levels by 10 months post-natally. In agreement with this, the only study to examine C4BP in preterm neonates found the levels (6% of adult levels) to be 3-times lower than term neonates (18% of adult levels) in newborns between 23 and 33 weeks gestation using the very sensitive RIA method (Malm et al 1988). Factor H levels in term neonates on average were 63.6% adult levels across studies, while fI levels were slightly lower with an average of 50.8%.…”

“…This activation leads to covalent "tagging" of the activating surface with C4b and C3b. C3b is further modified by factor I (fI) in the presence of complement receptor 1 (CR1 = CD35; present on erythrocytes and phagocytes) Davis et al (1979) T 10 61 55 Malm et al (1988) P 23-33 weeks 26 6 (RIA) Cat et al (1993) P to a covalently bound C3dg fragment. C3dg in turn is recognised by complement receptor 2 (CR2 = CD21), which is almost exclusively expressed on B-lymphocytes.…”

Protein C, protein S and C4b-binding protein in neonatal severe infection and septic shock

“…There are limited reports about these coagulation inhibitors under pathologic conditions during the neonatal period, however many authors have studied them in healthy infants [15,20,22,24,25]. PC, free and total PS have lower values in newborns compared to normal adults and PS circulates essentially in the free form [15,20].…”

C4b-Binding Protein, a Regulatory Component of the Classical Pathway of Complement, Is an Acute-Phase Protein and Is Elevated in Systemic Lupus Erythematosus

“…The adult serum concentration of C4BP has been reported to be 200 pg/ml using pooled serum [24], while fetal and newborn levels are only 5 and 20%, respectively, of adult levels [25][26][27], C4BP is hormonally regulated, with levels increasing slightly dur ing pregnancy [26][27][28] and in women in oral contraceptives [26,29,30], In humans there is no difference in C4BP serum levels be tween the sexes; however, in mice the levels are androgen regulated, with male mice hav ing 2.5-fold the levels of females [31]. There…”