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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.
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.
Background:
Critically ill children are susceptible to nosocomial infections, which contribute to adverse outcomes. Deficiencies in the innate immunity lectin pathway of complement activation are implicated in a child's vulnerability to infections in conditions such as cancer, but the role during critical illness remains unclear. We hypothesized that low on-admission levels of the pathway proteins are, in part, genetically determined and associated with susceptibility to infectious complications and adverse outcomes.
Methods:
We studied protein levels of mannose-binding lectin (MBL), H-ficolin and M-ficolin, three MBL-associated-serine proteases (MASPs) and MBL-associated protein (MAp44), and relation with functional genetic polymorphisms, in 130 healthy children and upon intensive care unit (ICU) admission in 700 critically ill children of a randomized study on glycemic control.
Results:
Levels of MASP-1, MASP-2, MASP-3, and MAp-44 were lower and the levels of M-ficolin were higher in ICU patients on admission than those in matched healthy controls. Only a low on-admission MASP-3 level was independently associated with risk of new ICU infections and prolonged ICU stay, after correcting for other risk factors. On-admission MASP-3 varied with age, illness severity, and genetic variation.
Conclusion:
Low on-admission MASP-3 levels in critically ill children were independently associated with subsequent acquisition of infection and prolonged ICU stay. The biological explanation needs further investigation.
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