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 and Experimental Medicine
Subjects: R Medicine > R Medicine (General)
R Medicine > RJ Pediatrics
Depositing User: Caroline Brooks
Date Deposited: 19 Aug 2011 14:37
Last Modified: 29 Nov 2017 16:35
URI: http://sro.sussex.ac.uk/id/eprint/7067
Google Scholar:78 Citations
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