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

Intensive Care Med. 2004 Jul;30(7):1438-45. doi: 10.1007/s00134-004-2303-8. Epub 2004 May 4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Cohort Studies
  • Exons / genetics
  • Female
  • Haplotypes
  • Humans
  • Incidence
  • Infant
  • Intensive Care Units, Pediatric
  • Male
  • Mannose-Binding Lectin / analogs & derivatives*
  • Mannose-Binding Lectin / blood
  • Mannose-Binding Lectin / genetics*
  • Polymorphism, Genetic / genetics
  • Prospective Studies
  • Risk Factors
  • Severity of Illness Index
  • Systemic Inflammatory Response Syndrome / epidemiology
  • Systemic Inflammatory Response Syndrome / genetics*
  • Systemic Inflammatory Response Syndrome / pathology
  • United Kingdom / epidemiology


  • MBL2 protein, human
  • Mannose-Binding Lectin