title: Increased incidence and severity of the systemic inflammatory response syndrome in patients deficient in mannose-binding lectin.
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.
  
  
  METHODS
  A prospective, observational cohort study in a 22-bed PICU in a tertiary referral centre.
  
  
  METHODS
  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.
  
  
  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.
authors.affiliation: Infectious Diseases and Microbiology Unit, Institute of Child Health, 30 Guilford Street, London, WC1 N 1EH, UK.
authors.forename: Katy J
authors.initials: KJ
authors.lastname: Fidler
authors.forename: Peter
authors.initials: P
authors.lastname: Wilson
authors.forename: Jane C
authors.initials: JC
authors.lastname: Davies
authors.forename: Malcolm W
authors.initials: MW
authors.lastname: Turner
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Peters
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Klein
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005091:Exons / Q000235:genetics; D005260:Female; D006239:Haplotypes; D006801:Humans; D015994:Incidence; D007223:Infant; D015278:Intensive Care Units, Pediatric; D008297:Male; D037601:Mannose-Binding Lectin / Q000031:analogs & derivatives* / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D011446:Prospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D018746:Systemic Inflammatory Response Syndrome / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D006113:United Kingdom / Q000453:epidemiology
chemical_list: C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin