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- Title
Increased incidence and severity of the systemic inflammatory response syndrome in patients deficient in mannose-binding lectin.
- Authors
Fidler, Katy J.; Wilson, Peter; Davies, Jane C.; Turner, Malcolm W.; Peters, Mark J.; Klein, Nigel J.
- Abstract
<bold>Objective: </bold>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.<bold>Design and Setting: </bold>A prospective, observational cohort study in a 22-bed PICU in a tertiary referral centre.<bold>Patients: </bold>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.<bold>Measurements and Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
LECTINS; HEMAGGLUTININ; IMMUNOGLOBULINS; GENETIC polymorphisms; PEDIATRICS; BLOOD plasma; COMPARATIVE studies; GENES; INTENSIVE care units; LONGITUDINAL method; RESEARCH methodology; MEDICAL cooperation; PROTEINS; RESEARCH; EVALUATION research; DISEASE incidence; SEVERITY of illness index; HAPLOTYPES; SYSTEMIC inflammatory response syndrome
- Publication
Intensive Care Medicine, 2004, Vol 30, Issue 7, p1438
- ISSN
0342-4642
- Publication type
journal article
- DOI
10.1007/s00134-004-2303-8