Low serum mannose-binding lectin level increases the risk of death due to pneumococcal infection.
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.
Eisen
Damon P
DP
Centre for Clinical Research Excellence in Infectious Diseases, Victorian Infectious Diseases Service, Royal Melbourne Hospital, Parkville, Victoria, Australia. damon.eisen@mh.org.au
Dean
Melinda M
MM
Boermeester
Marja A
MA
Fidler
Katy J
KJ
Gordon
Anthony C
AC
Kronborg
Gitte
G
Kun
Jürgen F J
JF
Lau
Yu Lung
YL
Payeras
Antonis
A
Valdimarsson
Helgi
H
Brett
Stephen J
SJ
Ip
W K Eddie
WK
Mila
Joan
J
Peters
Mark J
MJ
Saevarsdottir
Saedis
S
van Till
J W Oliver
JW
Hinds
Charles J
CJ
McBryde
Emma S
ES
D018806:APACHE; D000328:Adult; D016470:Bacteremia / Q000276:immunology / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D005838:Genotype; D006801:Humans; D037601:Mannose-Binding Lectin / Q000097:blood* / Q000235:genetics; D011008:Pneumococcal Infections / Q000276:immunology / Q000401:mortality*; D011237:Predictive Value of Tests; D012372:ROC Curve; D012307:Risk Factors
D037601:Mannose-Binding Lectin