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Genetic variability in complement activation modulates the systemic inflammatory response syndrome in children

Rachel S Agbeko1, Katy J Fidler, Meredith L Allen

  • 1Paediatric Intensive Care Unit, Great Ormond Street Hospital NHS Trust, London, United Kingdom. r.agbeko@ich.ucl.ac.uk

Pediatric Critical Care Medicine : a Journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies
|March 31, 2010
PubMed

Insights

Genetic variations in complement activation impact systemic inflammatory response syndrome (SIRS) in critically ill children. Certain complement factor H variants protect against SIRS, while mannose-binding lectin variants increase risk.

Area of Science:

  • Immunogenetics
  • Pediatric Critical Care
  • Systemic Inflammation

Background:

  • The complement system plays a crucial role in innate immunity and inflammation.
  • Genetic variability in complement pathways may influence susceptibility to severe inflammatory conditions like SIRS.
  • Understanding these genetic factors is vital for predicting and managing SIRS in pediatric intensive care.

Purpose of the Study:

  • To investigate the association between genetic polymorphisms in complement activation and the early development of SIRS in pediatric critical care.
  • To identify specific complement genes that act as modifiers of SIRS risk in children.

Main Methods:

  • Prospective observational cohort study conducted in a UK tertiary pediatric intensive care unit.
  • Genotyping of 299 children for functional polymorphisms in the complement activation cascade.
  • Analysis of genetic variants, including complement factor H (CFH) and mannose-binding lectin (MBL), in relation to SIRS development.

Main Results:

  • Complement factor H (CFH) was identified as a significant genetic modifier of SIRS/sepsis.
  • Homozygosity for the CFH Y402H polymorphism was associated with a reduced risk of SIRS/sepsis (OR 0.3, p=0.005).
  • Mannose-binding lectin (MBL) genotypes were confirmed as a risk factor for SIRS/sepsis (OR 2.5, p=0.008), independent of clinical factors.

Conclusions:

  • Functional polymorphisms in complement activation pathways significantly modify SIRS/sepsis risk in pediatric critical care.
  • The CFH Y402H variant allele appears protective against SIRS, whereas MBL variant polymorphisms increase risk.
  • Vigorous complement activation, influenced by specific genotypes, may confer protection against systemic inflammation.
Abstract

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