Mannose-Binding Lectin Levels in Critically Ill Children With Severe Infections

Pediatr Crit Care Med. 2017 Feb;18(2):103-111. doi: 10.1097/PCC.0000000000001000.

Abstract

Objectives: Low mannose-binding lectin levels and haplotypes associated with low mannose-binding lectin production have been associated with infection and severe sepsis. We tested the hypothesis that mannose-binding lectin levels would be associated with severe infection in a large cohort of critically ill children.

Design: Prospective cohort study.

Setting: Medical and Surgical PICUs, Boston Children's Hospital.

Patients: Children less than 21 years old admitted to the ICUs from November 2009 to November 2010.

Interventions: None.

Measurements and main results: We measured mannose-binding lectin levels in 479 of 520 consecutively admitted children (92%) with severe or life-threatening illness. We genotyped 213 Caucasian children for mannose-binding lectin haplotype tagging variants and assigned haplotypes. In the univariate analyses of mannose-binding lectin levels with preadmission characteristics, levels were higher in patients with preexisting renal disease. Patients who received greater than 100 mL/kg of fluids in the first 24 hours after admission had markedly lower mannose-binding lectin, as did patients who underwent spinal fusion surgery. Mannose-binding lectin levels had no association with infection status at admission, or with progression from systemic inflammatory response syndrome to sepsis or septic shock. Although mannose-binding lectin haplotypes strongly influenced mannose-binding lectin levels in the predicted relationship, low mannose-binding lectin-producing haplotypes were not associated with increased risk of infection.

Conclusions: Mannose-binding lectin levels are largely genetically determined. This relationship was preserved in children during critical illness, despite the effect of large-volume fluid administration on mannose-binding lectin levels. Previous literature evaluating an association between mannose-binding lectin levels and severe infection is inconsistent; we found no relationship in our PICU cohort. We found that mannose-binding lectin levels were lower after aggressive fluid resuscitation and suggest that studies of mannose-binding lectin in critically ill patients should assess mannose-binding lectin haplotypes to reflect preillness levels.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Biomarkers / blood
  • Child
  • Child, Preschool
  • Critical Illness
  • Female
  • Genetic Markers
  • Genotyping Techniques
  • Haplotypes*
  • Humans
  • Immunity, Innate*
  • Infant
  • Infant, Newborn
  • Male
  • Mannose-Binding Lectin / blood*
  • Mannose-Binding Lectin / genetics
  • Polymorphism, Single Nucleotide*
  • Prospective Studies
  • Sepsis / blood
  • Sepsis / diagnosis
  • Sepsis / genetics
  • Sepsis / immunology*
  • Severity of Illness Index
  • Young Adult

Substances

  • Biomarkers
  • Genetic Markers
  • MBL2 protein, human
  • Mannose-Binding Lectin