Differential role of the lectin pathway of complement activation in susceptibility to neonatal sepsis.
Schlapbach, L et al. CID 2010, 51:153
Incidence of bacterial sepsis during the neonatal period:
The incidence of bacterial sepsis during the neonatal period is high. Innate immunity plays an important role in the defense of neonates against invasive infections. Mannan-binding lectin (MBL), L-ficolin, and H-ficolin recognize microorganisms and activate the complement system via MBL-associated serine proteases (MASPs). However, the entire lectin pathway has never been studied in patients with sepsis.
Cord blood concentrations of the lectin proteins:
This study investigated whether cord blood concentrations of the lectin pathway proteins are associated with neonatal sepsis. This was a case-control study including 47 infants with culture-proven sepsis during the first month of life and 94 matched controls. Lectin pathway concentrations were measured in cord blood with use of enzyme-linked immunosorbent assay (MBL, L-ficolin, MASP-2) and time-resolved immunofluorometric assay (H-ficolin, MASP-3). Multivariate logistic regression was performed.
Different results infants with gram-positive and gram-negative sepsis:
Infants with gram-positive sepsis had significantly lower H-ficolin cord blood concentrations than controls (multivariate odds ratio [OR], 4.00; 95% confidence interval [CI], 1.51–10.56;p=.005), whereas infants with gram-negative sepsis had lower MBL cord blood concentrations (OR, 2.99; 95% CI, 0.86–10.33; p=.084).
When excluding patients with postoperative sepsis, multivariate analysis confirmed that low H-ficolin was associated with a significantly higher risk of gram-positive sepsis (OR, 3.71; 95% CI, 1.26–10.92; p=.017) and late-onset sepsis (OR, 3.14; 95% CI, 1.07–9.21; p=.037). In contrast, low MBL was associated with a significantly higher risk of gram-negative sepsis (OR, 4.39; 95% CI, 1.10–17.45; p=.036) and early-onset sepsis (OR, 3.87; 95% CI, 1.05–14.29; p=.042). The concentrations of all the lectin pathway proteins increased with gestational age (p< 0.01).
Conclusions:
These results indicate that low MBL concentrations are a susceptibility factor for gram-negative sepsis, and low H-ficolin concentrations indicate susceptibility to gram-positive sepsis. The decreased expression of lectin pathway proteins in neonates must be considered to be an additional form of neonatal immunodeficiency.