Increased incidence and severity of the systemic inflammatory response syndrome in patients deficient in mannose-binding lectin

Fidler, Katy J., Wilson, Peter, Davies, Jane C., Turner, Malcolm W., Peters, Mark J. and Klein, Nigel J. (2004) Increased incidence and severity of the systemic inflammatory response syndrome in patients deficient in mannose-binding lectin. Intensive Care Medicine, 30 (7). pp. 1438-1445. ISSN 0342-4642

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Abstract

Objective
To determine whether pediatric PICU patients with mannose-binding lectin (MBL) gene polymorphisms associated with low levels of the functional protein have an increased risk of developing sepsis and SIRS.
Design and setting
A prospective, observational cohort study in a 22-bed PICU in a tertiary referral centre.
Patients
One hundred consecutive admissions to a PICU with at least one organ system failure longer than 12 h. Patients were classified into those with infectious or non-infectious insults as the primary reason for intensive care admission. Patients were followed to determine which developed sepsis or non-infection related SIRS using standard criteria.
Measurements and results
Of the 100 patients 50 had infectious and 50 had non-infectious insults as the precipitant for admission. 42 patients had variant MBL alleles (determined by MBL-2 gene exon 1 and promoter polymorphisms) and were significantly over-represented amongst the 59 patients that developed SIRS. This effect was not explained by differences in age, sex or ethnicity and was seen in both the infection and non-infection subgroups. In patients with infection, variant MBL alleles were associated with increased systemic response (2/15 with localised infection, 10/19 with sepsis and 12/16 with septic shock). MBL serum levels showed close concordance with the genotype and indicated that MBL levels less than 1000 ng/ml are associated with a greatly increased risk of SIRS.
Conclusions
MBL-2 exon 1 polymorphisms with low serum levels of functional MBL protein are associated with a greatly increased risk of developing SIRS and of progression from infection to sepsis and septic shock in paediatric ICU patients.

Item Type: Article
Additional Information: IDS Number: 832AO
Keywords: Systemic inflammatory response syndrome - Sepsis - Mannose-binding lectin - Complement
Schools and Departments: Brighton and Sussex Medical School > Clinical Medicine
Subjects: R Medicine > R Medicine (General)
R Medicine > RJ Pediatrics
Depositing User: Caroline Brooks
Date Deposited: 19 Aug 2011 14:37
Last Modified: 30 Nov 2012 16:55
URI: http://sro.sussex.ac.uk/id/eprint/7067
Google Scholar:78 Citations
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