Evaluation of complement activation in premature newborn infants with hyaline membrane disease

Abstract

Fifteen premature newborns with hyaline membrane disease causing acute respiratory distress were evaluated for complement activation. A high intrapulmonary right-to-left shunt and marked arterial-alveolar oxygen difference indicated the severity of the respiratory failure. Twenty preterm healthy infants served as controls. Total haemolytic activity, plasma concentrations of complement components and regulatory proteins (C3, C4, C1-inhibitor, factors H and I) as well as activation products (C3a, C3dg, C1rsC1-inhibitor, C3b(Bb)P) gave no evidence of significant complement activation. Functional activity of the ubiquitous regulatory protein C1-inhibitor was significantly reduced without impact on classical pathway activation. These data suggest that, in contrast to the adult form of respiratory distress syndrome, the low-pressure pulmonary oedema characterising hyaline membrane disease is not mediated by activation of the complement system.

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

“…Davis et al (1979) also indicated that these levels were still lower than adult levels at 6 months after birth. These fH and fI levels were not substantially lower in the 27-37 week gestation preterm neonates reported by Cat et al (1993), than the levels in term neonates.…”

“…levels and that the C1 inhibitor levels were reduced, rather than elevated, in the mothers relative to non-pregnant controls. Cat et al (1993) subsequently studied C1 inhibitor levels in preterm infants and reported a mean of 17.5 ± 6.0 U/ml functional titre but only indicated that relative to the control adult serum values the range was 42-84%. Relative to adult serum, C4BP levels in normal term neonates is very low and in some studies lower than the threshold of detection (de Paula et al 2003).…”

“…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.…”

“…Johnson et al (1983) -percentages have been calculated from Geometric Mean values. Sonntag et al (1998a) -percentages have been calculated using mid-range values from newborn and adult reference ranges.To analyse complement components, radial immunodiffusion is the method used in all of the above studies except where indicated: RIA = radio immunoassay, LRE = Laurell rocket immunoassay, IE = immunoelectrophoresis Cat et al (1993). only listed the values as a range of normal serum values.a The values in parentheses were compared to maternal serum, which are not identical to normal serum levelsJohnson et al (1983) andAdinolfi et al (1981).…”

Complement activation in infective endocarditis: correlation with extracardiac manifestations and prognosis

“…C1rs‐C1Inh and C3b(Bb)P. Specific activation of the classical and alternative pathways was analysed by measuring the protein–protein complexes C1rs‐C1inhibitor (C1rs‐C1Inh) and C3b(Bb)P, respectively, by ELISA, basically as described in Cat et al 1993 [20]. Briefly, microtitre plates (Nunc) were coated with rabbit antiC1Inh IgG (Dakopatts) or goat antiproperdin IgG (Baxter, Unterschleisheim, Germany).…”