M-ficolin concentrations in cord blood are related to circulating phagocytes and to early-onset sepsis.

INTRODUCTION: The pattern-recognition molecule M-ficolin is synthesized by monocytes and neutrophils. M-ficolin activates the complement system in a manner similar to mannan-binding lectin (MBL), but little is known about its role in host defense. Neonates are highly vulnerable to bacterial sepsis, in particular, due to their decreased phagocytic function. RESULTS: M-ficolin cord blood concentration was positively correlated with the absolute phagocyte count (ρ 0.51, P < 0.001) and with immature/total neutrophil ratio (ρ 0.34, P < 0.001). When comparing infants with sepsis and controls, a high M-ficolin cord blood concentration (>1,000 ng/ml) was associated with early-onset sepsis (EOS) (multivariate odds ratio 10.92, 95% confidence interval 2.21-54.02, P = 0.003). Experimental exposure of phagocytes isolated from adult donors to Escherichia coli resulted in a significant time- and dose-dependent release of M-ficolin. DISCUSSION: In conclusion, M-ficolin concentrations were related to circulating phagocytes and EOS. Our results indicate that bacterial sepsis can trigger M-ficolin release by phagocytes. Future studies should investigate whether M-ficolin may be used as a marker of neutrophil activation during invasive infections. METHODS: We investigated M-ficolin in 47 infants with culture-positive sepsis during the first 30 days of life (13 with EOS and in 94 matched controls. M-ficolin was measured in cord blood using time-resolved immunofluorometric assay (TRIFMA). Multivariate logistic regression was performed.

Differential role of the lectin pathway of complement activation in susceptibility to neonatal sepsis.

BACKGROUND. The incidence of bacterial sepsis during the neonatal period is high. Mannan-binding lectin (MBL), L-ficolin, and H-ficolin recognize microorganisms and activate the complement system via MBL-associated serine proteases (MASPs). This study investigated whether cord blood concentrations of the lectin pathway proteins are associated with neonatal sepsis. METHODS. This was a case-control study including 47 infants with culture-proven sepsis during the first month of life and 94 matched controls. MBL, L-ficolin, H-ficolin, MASP-2, and MASP-3 levels were measured in cord blood with use of enzyme-linked immunosorbent assay and time-resolved immunofluorometric assay. Multivariate logistic regression was performed. RESULTS. 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 < .01). CONCLUSIONS. These preliminary 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.