Biochemical abnormalities of the third component of complement in neonates.
The third component of complement, C3, is of central importance as an opsonin in the nonimmune host. Although gestational deficiencies in C3 levels are well recognized in neonates, defects in complement-mediated functions have not in every case correlated with low levels of complement proteins. Because opsonic functions of C3 are mediated through a reactive thiolester bond, we hypothesized that a biochemical dysfunction at this active site could explain the newborn's predisposition to infection, even with relatively normal C3 levels. We therefore examined the biochemical integrity of the C3 thiolester in an assay independent of all other complement proteins. As measured by ELISA, mean C3 levels from 44 neonates (24-43 wk) were significantly lower in infants less than 30 wk gestational age (0.79 +/- 0.13 mg/mL) than in full-term newborns (1.19 +/- 0.27 mg/ml, p less than 0.05). Furthermore, biochemical reactivity of the thiolester bond, as measured by incorporation of the radiolabeled nucleophile, methylamine, correlated significantly with gestational age (r = 0.45, p less than 0.01). Functional C3 was defined as the product of thiolester reactivity and C3 level; 9/11 premature and 2/17 full-term infants had levels of functional C3 which were less than 50% of the adult norm. Structural analysis of neonatal C3 revealed the two-chain structure in all neonates; four neonates had an additional band at 205 kD which may represent an impairment in posttranslational processing of a precursor molecule. We conclude that defects in thiolester reactivity may constitute a newly identified mechanism for the newborn's susceptibility to infection.
Division of Neonatology, University of Minnesota, Minneapolis 55455.
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Hostetter
D001778:Blood Coagulation Disorders / Q000209:etiology*; D002846:Chromatography, Affinity; D003176:Complement C3 / Q000032:analysis*; D004797:Enzyme-Linked Immunosorbent Assay; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn / Q000097:blood*
D003176:Complement C3