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



Prospective cohort study.



Medical and Surgical PICUs, Boston Children's Hospital.



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



None.



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.



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.
1Division of Critical Care Medicine, Department of Anesthesia, Perioperative and Pain Medicine, Boston, MA. 2Division of Critical Care Medicine, Department of Pediatrics, Duke University, Durham, NC. 3Department of Anesthesia, Harvard Medical School, Boston, MA. 4Department of Pediatrics, Harvard Medical School, Boston, MA. 5Department of Pediatrics, Center for Patient Safety and Quality Research, Boston Children's Hospital, Boston, MA.
Erik C
EC
Madsen
Emily R
ER
Levy
Kate
K
Madden
Anna A
AA
Agan
Ryan M
RM
Sullivan
Dionne A
DA
Graham
Adrienne G
AG
Randolph
D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D016638:Critical Illness; D005260:Female; D005819:Genetic Markers; D060005:Genotyping Techniques; D006239:Haplotypes; D006801:Humans; D007113:Immunity, Innate; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D037601:Mannose-Binding Lectin / Q000097:blood* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D018805:Sepsis / Q000097:blood / Q000175:diagnosis / Q000235:genetics / Q000276:immunology*; D012720:Severity of Illness Index; D055815:Young Adult
D015415:Biomarkers; D005819:Genetic Markers; C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin