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

Abstract

Objective Low mannose-binding lectin (MBL) levels and haplotypes associated with low MBL production have been associated with infection and severe sepsis. We tested the hypothesis that MBL levels would be associated with severe infection in a large cohort of critically ill children. Design Prospective cohort study Setting Medical and Surgical Pediatric Intensive Care Units (PICUs), Boston Children’s Hospital Patients Children < 21 years of age admitted to the intensive care units from November 2009 to November 2010. Interventions None Measurements and Main Results We measured MBL levels in 479/520 (92%) consecutively admitted children with severe or life-threatening illness. We genotyped 213 Caucasian children for MBL haplotype tagging variants and assigned haplotypes. In the univariate analyses of MBL levels with pre-admission characteristics, levels were higher in patients with pre-existing renal disease. Patients who received >100 ml/kg of fluids in the first 24 hours after admission had markedly lower MBL, as did patients post-spinal fusion surgery. MBL levels had no association with infection status on admission, or with progression from systemic inflammatory response syndrome to sepsis or septic shock. Although MBL haplotypes strongly influenced MBL levels in the predicted relationship, low MBL-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 MBL levels. Previous literature evaluating an association between MBL levels and severe infection is inconsistent; we found no relationship in our PICU cohort. We found that MBL levels were lower after aggressive fluid resuscitation, and suggest that studies of MBL in critically ill patients should assess MBL haplotypes to reflect pre-illness levels.

Evaluation of Mannose Binding Lectin Gene Variants in Pediatric Influenza Virus-Related Critical Illness

“…A large cohort of hospitalized children with meningococcemia also did not have higher carriage of O alleles (49). In single center nested case-control PICU studies, we reported no differences in carriage of low-producing MBL2 variants in patients with severe infections (22) but others reported a 2-fold overall increase in carriage of the O allele with an increase in homozygotes (50). Although MBL2 haplotypes associated with deficiency appear to be a risk factor for a range of infections in neonates or other immune compromised patients, our study adds to the literature that carriage of low-producing MBL2 variants does not increase risk of severe viral infections (51).…”

“…MBL deficiency is common, and may occur in 30% of the population depending on what MBL level cutoff is used for defining it; deficiency has been defined variably as <1,000, <500, <200, or <100 ng/mL (21). In critically ill patients, serum levels may be influenced by inflammation, diluted by fluid resuscitation, or raised via fresh frozen plasma transfusion, so genotype has been used as an inexact proxy to estimate pre-illness MBL deficiency (17, 22).…”

Respiratory outcomes at five-year follow-up in children with MBL deficiency: a cohort study

“…However in a recent study, MBL levels had no association with infection status at admission, or with progression from systemic inflammatory response syndrome to sepsis or septic shock in children admitted with severe or life-threatening illness 16 . It has also been shown that MBL deficiency is not associated with a susceptibility to influenza-related critical illness in children 17 .…”

A SNaPshot Assay for Determination of the Mannose-Binding Lectin Gene Variants and an Algorithm for Calculation of Haplogenotype Combinations

“…Up to this day, a wide spectrum of other methods have been used for detection of MBL2 gene variants, including commercially available TaqMan assays [ 27 ], high-resolution melt analysis (HRMA) [ 28 ], reverse hybridization with membrane-immobilized sequence-specific oligonucleotide probes (reverse PCR-SSOP) [ 29 ], PCR with sequence-specific primers (SSP-PCR) [ 30 , 31 ], PCR and restriction-fragment length polymorphism (PCR-RFLP) analysis [ 32 ], an oligonucleotide ligation assay [ 33 , 34 ], a single-strand conformation polymorphism technique (PCR-SSCP) [ 35 ], the iPLEX assay on a MassArray system [ 36 ], Sanger sequencing [ 37 ], and pyrosequencing [ 38 ].…”