Lectin pathway of complement activation and relation with clinical complications in critically ill children

Catherine Ingels1, Ilse Vanhorebeek1, Rudi Steffensen2

  • 1Clinical Department and Laboratory of Intensive Care Medicine, Division of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.

Pediatric Research
|October 17, 2013
PubMed

Insights

Low levels of MASP-3, a complement pathway protein, upon intensive care unit (ICU) admission in children are linked to increased risk of new infections and longer ICU stays. This finding highlights potential biomarkers for infection risk in critically ill children.

Area of Science:

  • Immunology
  • Critical Care Medicine
  • Genetics

Background:

  • Critically ill children face high risks of hospital-acquired infections, impacting outcomes.
  • Deficiencies in the innate immune lectin complement pathway are linked to infection susceptibility, but their role in critical illness is not well understood.
  • This study investigated if low levels of lectin pathway proteins upon admission are genetically influenced and associated with infection risk.

Purpose of the Study:

  • To determine the association between on-admission levels of lectin pathway complement proteins and the risk of infectious complications in critically ill children.
  • To explore the genetic determination of these protein levels.
  • To identify potential biomarkers for predicting infection risk and outcomes in the ICU.

Main Methods:

  • Measured protein levels of mannose-binding lectin (MBL), H-ficolin, M-ficolin, MBL-associated-serine proteases (MASPs), and MBL-associated protein (MAp44).
  • Analyzed these levels in 700 critically ill children upon ICU admission and compared them to 130 healthy children.
  • Correlated protein levels with functional genetic polymorphisms and clinical outcomes, including new ICU infections and ICU stay duration.

Main Results:

  • Critically ill children had lower MASP-1, MASP-2, MASP-3, and MAp-44 levels and higher M-ficolin levels compared to healthy controls.
  • Low on-admission MASP-3 levels were independently associated with an increased risk of new ICU infections and prolonged ICU stay.
  • On-admission MASP-3 levels were influenced by age, illness severity, and genetic variations.

Conclusions:

  • Low MASP-3 levels at ICU admission are a significant independent predictor of subsequent infections and extended ICU stays in critically ill children.
  • These findings suggest MASP-3 as a potential biomarker for infection risk stratification.
  • Further research is needed to elucidate the underlying biological mechanisms connecting MASP-3 levels to infection susceptibility and outcomes.
Abstract

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