Springer, Intensive Care Medicine, 7(30), p. 1438-1445, 2004
DOI: 10.1007/s00134-004-2303-8
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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.