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

Luregn J Schlapbach1, Maika Mattmann, Steffen Thiel

  • 1Departments of Pediatrics, University of Bern, Bern, Switzerland. luregn.schlapbach@insel.ch

Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America
|June 10, 2010
PubMed

Insights

Low cord blood concentrations of Mannan-binding lectin (MBL) increase the risk of gram-negative neonatal sepsis, while low H-ficolin is linked to gram-positive sepsis. These findings suggest neonatal immunodeficiency may be influenced by lectin pathway protein levels.

Area of Science:

  • Immunology
  • Neonatal Medicine
  • Infectious Diseases

Background:

  • Neonatal sepsis incidence is high, posing a significant threat to newborns.
  • The lectin complement pathway, involving Mannan-binding lectin (MBL), L-ficolin, and H-ficolin, plays a role in recognizing and clearing microorganisms.
  • MBL-associated serine proteases (MASPs) are crucial for activating this pathway.

Purpose of the Study:

  • To investigate the association between cord blood concentrations of lectin pathway proteins and the risk of developing neonatal sepsis.
  • To determine if specific lectin pathway protein deficiencies correlate with different types of bacterial sepsis (Gram-positive vs. Gram-negative).

Main Methods:

  • A case-control study was conducted with 47 infants diagnosed with culture-proven sepsis and 94 matched controls.
  • Cord blood levels of MBL, L-ficolin, H-ficolin, MASP-2, and MASP-3 were quantified using enzyme-linked immunosorbent assay and time-resolved immunofluorometric assay.
  • Multivariate logistic regression analysis was employed to assess the associations.

Main Results:

  • Significantly lower H-ficolin cord blood concentrations were observed in infants with Gram-positive sepsis compared to controls.
  • Lower MBL cord blood concentrations were associated with an increased risk of Gram-negative sepsis.
  • Low H-ficolin was linked to higher risks of Gram-positive and late-onset sepsis, while low MBL correlated with higher risks of Gram-negative and early-onset sepsis.
  • All measured lectin pathway proteins showed increased concentrations with higher gestational age.

Conclusions:

  • Low MBL cord blood levels may indicate susceptibility to Gram-negative neonatal sepsis.
  • Low H-ficolin cord blood levels suggest a predisposition to Gram-positive neonatal sepsis.
  • Reduced expression of lectin pathway proteins in neonates could represent an additional form of neonatal immunodeficiency, impacting their defense against infections.

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