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

journal contribution
posted on 2023-06-16, 06:41 authored by Rachel S Agbeko, Katy FidlerKaty Fidler, Meredith L Allen, Peter Wilson, Nigel Klein, Mark J Peters
Objective: To determine the impact of genetic variability in complement activation on early development of the systemic inflammatory response syndrome (SIRS) in general pediatric critical care. Design: Prospective, observational, cohort study. Setting: A tertiary pediatric intensive care unit in the United Kingdom. Patients: Children with at least one organ failure expected to stay in the intensive care unit >12 hrs, or an expected death within 12 hrs. Interventions: None. Measurements and Main results: A total of 299 children were genotyped for functional polymorphisms in the complement activation cascade. We identified complement factor H as an important independent genetic modifier of SIRS/sepsis. Homozygosity for the complement factor H Y402H polymorphism, which is thought to reduce complement inhibition, was associated with less frequent SIRS/sepsis (the adjusted odds ratio for the homozygous variant complement factor H Y402H [CC] carriers was 0.3, 95% confidence interval, 0.1–0.7, p = .005). We also confirmed that structural and promoter variant mannose-binding lectin genotypes are a risk factor for SIRS/sepsis in pediatric critical care (adjusted odds ratio, 2.5; 95% confidence interval, 1.3–5.0, p = .008). Both findings were independent of clinical characteristics and other potentially confounding genetic polymorphisms in the innate immune system. Conclusions: Functional polymorphisms in the complement activation cascade modify the risk for early SIRS/sepsis in general pediatric critical care. The complement factor H Y402H variant allele is protective, whereas the mannose-binding lectin variant polymorphisms increase risk. A genotype that permits vigorous complement activation to an infectious or inflammatory insult may offer protection from development of systemic inflammation.


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  • Published


Pediatric Critical Care Medicine




Lippincott, Williams & Wilkins





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  • Clinical and Experimental Medicine Publications

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