Low serum mannose‐binding lectin level increases the risk of death due to pneumococcal infection

Eisen, Damon P., Dean, Melinda M., Boermeester, Marja A., Fidler, Katy J., Gordon, Anthony C., Kronborg, Gitte, Kun, Jürgen F.J., Lau, Yu Lung, Payeras, Antonis, Valdimarsson, Helgi, Brett, Stephen J., Mila, Joan, Ip, W.K. Eddie, Peters, Mark J., Saevarsdottir, Saedis, van Till, J.W. Oliver, Hinds, Charles J., and McBryde, Emma S. (2008) Low serum mannose‐binding lectin level increases the risk of death due to pneumococcal infection. Clinical Infectious Diseases, 47 (4). pp. 510-516.

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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 BL concentrations. Receiver operating characteristic analysis revealed that an MBL cutoff value of 0.5 mg/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.

Item ID: 39781
Item Type: Article (Research - C1)
ISSN: 1537-6591
Funders: National Institute of Health Research
Date Deposited: 08 Sep 2015 03:55
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110309 Infectious Diseases @ 40%
11 MEDICAL AND HEALTH SCIENCES > 1117 Public Health and Health Services > 111706 Epidemiology @ 40%
16 STUDIES IN HUMAN SOCIETY > 1605 Policy and Administration > 160508 Health Policy @ 20%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 60%
92 HEALTH > 9203 Indigenous Health > 920309 Pacific Peoples Health - Health System Performance (incl. Effectiveness of Interventions) @ 20%
92 HEALTH > 9202 Health and Support Services > 920207 Health Policy Evaluation @ 20%
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