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

Agbeko, Rachel S, Fidler, Katy J, Allen, Meredith L, Wilson, Peter, Klein, Nigel and Peters, Mark J (2010) Genetic variability in complement activation modulates the systemic inflammatory response syndrome in children. Pediatric Critical Care Medicine, 11 (5). pp. 561-567. ISSN 1529-7535

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Abstract

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.

Item Type: Article
Keywords: complement activation, child, systemic inflammatory response syndrome, sepsis, genetic polymorphism
Schools and Departments: Brighton and Sussex Medical School > Clinical and Laboratory Investigation
Subjects: R Medicine > R Medicine (General)
R Medicine > RJ Pediatrics
Depositing User: Caroline Brooks
Date Deposited: 19 Aug 2011 14:31
Last Modified: 02 Nov 2012 09:23
URI: http://sro.sussex.ac.uk/id/eprint/7068
Google Scholar:2 Citations
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