Low Serum Mannose-Binding Lectin Level Increases the Risk of Death due to Pneumococcal Infection
Damon P. Eisen,Melinda M. Dean,Marja A. Boermeester,Katy Fidler,Anthony C. Gordon,Gitte Kronborg,Jürgen F J Kun,Yu-Lung Lau,Antonis Payeras,Helgi Valdimarsson,Stephen J. Brett,W. K. Eddie Ip,Joan Mila,Mark J. Peters,Saedis Saevarsdottir,J W Oliver van Till,Charles J. Hinds,Emma S. McBryde +17 more
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TLDR
A serum level for MBL deficiency is defined that can be used with confidence in future studies of MBL disease associations, highlighting the pathogenic significance of this innate immune defence protein.Abstract:
BACKGROUND
Previous studies have shown associations between low mannose-binding lectin (MBL) level or variant MBL2 genotype and sepsis susceptibility. However, MBL deficiency has not been rigorously defined, and associations with sepsis outcomes have not been subjected to multivariable analysis.
METHODS
We reanalyzed MBL results in a large cohort with use of individual data from 4 studies involving a total of 1642 healthy control subjects and systematically defined a reliable deficiency cutoff. Subsequently, data were reassessed to extend previous MBL and sepsis associations, with adjustment for known outcome predictors. We reanalyzed individual data from 675 patients from 5 adult studies and 1 pediatric study of MBL and severe bacterial infection.
RESULTS
XA/O and O/O MBL2 genotypes had the lowest median MBL concentrations. Receiver operating characteristic analysis revealed that an MBL cutoff value of 0.5 microg/mL was a reliable predictor of low-producing MBL2 genotypes (sensitivity, 82%; specificity, 82%; negative predictive value, 98%). MBL deficiency was associated with increased likelihood of death among patients with severe bacterial infection (odds ratio, 2.11; 95% confidence interval, 1.30-3.43). In intensive care unit-based studies, there was a trend toward increased risk of death among MBL-deficient patients (odds ratio, 1.58; 95% confidence interval, 0.90-2.77) after adjustment for Acute Physiology and Chronic Health Enquiry II score. The risk of death was increased among MBL-deficient patients with Streptococcus pneumoniae infection (odds ratio, 5.62; 95% confidence interval, 1.27-24.92) after adjustment for bacteremia, comorbidities, and age.
CONCLUSIONS
We defined a serum level for MBL deficiency that can be used with confidence in future studies of MBL disease associations. The risk of death was increased among MBL-deficient patients with severe pneumococcal infection, highlighting the pathogenic significance of this innate immune defence protein.read more
Citations
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A Tick Mannose-Binding Lectin Inhibitor Interferes with the Vertebrate Complement Cascade to Enhance Transmission of the Lyme Disease Agent
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References
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Intensive Insulin Therapy Exerts Antiinflammatory Effects in Critically Ill Patients and Counteracts the Adverse Effect of Low Mannose-Binding Lectin Levels
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Impact of Mannose-Binding Lectin on Susceptibility to Infectious Diseases
Damon P. Eisen,R. M. Minchinton +1 more
TL;DR: Clinical studies have shown that MBL insufficiency is associated with bacterial infection in patients with neutropenia and meningococcal sepsis, and low MBL levels appear to predispose persons to HIV infection.
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