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 J. Fidler, Anthony C. Gordon, Gitte Kronborg, Jürgen F.J. Kun, Lung Lau Yu, Antonis Payeras, Helgi Valdimarsson, Stephen J. Brett, Wai Kee Eddie Ip, Joan Mila, Mark J. Peters, Saedis Saevarsdottir, J. W.Oliver Van Till, Charles J. Hinds, Emma S. McBryde

Research output: Contribution to journalArticle

138 Citations (Scopus)

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 μg/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.

Original languageEnglish (US)
Pages (from-to)510-516
Number of pages7
JournalClinical Infectious Diseases
Volume47
Issue number4
DOIs
StatePublished - Aug 15 2008
Externally publishedYes

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Mannose-Binding Lectin
Pneumococcal Infections
Serum
Sepsis
Odds Ratio
Genotype
Confidence Intervals
Bacterial Infections
Bacteremia
ROC Curve
Intensive Care Units
Comorbidity
Healthy Volunteers
Pediatrics

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Eisen, D. P., Dean, M. M., Boermeester, M. A., Fidler, K. J., Gordon, A. C., Kronborg, G., ... McBryde, E. S. (2008). Low serum mannose-binding lectin level increases the risk of death due to pneumococcal infection. Clinical Infectious Diseases, 47(4), 510-516. https://doi.org/10.1086/590006

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.; Yu, Lung Lau; Payeras, Antonis; Valdimarsson, Helgi; Brett, Stephen J.; Ip, Wai Kee Eddie; Mila, Joan; Peters, Mark J.; Saevarsdottir, Saedis; Van Till, J. W.Oliver; Hinds, Charles J.; McBryde, Emma S.

In: Clinical Infectious Diseases, Vol. 47, No. 4, 15.08.2008, p. 510-516.

Research output: Contribution to journalArticle

Eisen, DP, Dean, MM, Boermeester, MA, Fidler, KJ, Gordon, AC, Kronborg, G, Kun, JFJ, Yu, LL, Payeras, A, Valdimarsson, H, Brett, SJ, Ip, WKE, Mila, J, Peters, MJ, Saevarsdottir, S, Van Till, JWO, Hinds, CJ & McBryde, ES 2008, 'Low serum mannose-binding lectin level increases the risk of death due to pneumococcal infection', Clinical Infectious Diseases, vol. 47, no. 4, pp. 510-516. https://doi.org/10.1086/590006
Eisen DP, Dean MM, Boermeester MA, Fidler KJ, Gordon AC, Kronborg G et al. Low serum mannose-binding lectin level increases the risk of death due to pneumococcal infection. Clinical Infectious Diseases. 2008 Aug 15;47(4):510-516. https://doi.org/10.1086/590006
Eisen, Damon P. ; Dean, Melinda M. ; Boermeester, Marja A. ; Fidler, Katy J. ; Gordon, Anthony C. ; Kronborg, Gitte ; Kun, Jürgen F.J. ; Yu, Lung Lau ; Payeras, Antonis ; Valdimarsson, Helgi ; Brett, Stephen J. ; Ip, Wai Kee Eddie ; Mila, Joan ; Peters, Mark J. ; Saevarsdottir, Saedis ; Van Till, J. W.Oliver ; Hinds, Charles J. ; McBryde, Emma S. / Low serum mannose-binding lectin level increases the risk of death due to pneumococcal infection. In: Clinical Infectious Diseases. 2008 ; Vol. 47, No. 4. pp. 510-516.
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T1 - Low serum mannose-binding lectin level increases the risk of death due to pneumococcal infection

AU - Eisen, Damon P.

AU - Dean, Melinda M.

AU - Boermeester, Marja A.

AU - Fidler, Katy J.

AU - Gordon, Anthony C.

AU - Kronborg, Gitte

AU - Kun, Jürgen F.J.

AU - Yu, Lung Lau

AU - Payeras, Antonis

AU - Valdimarsson, Helgi

AU - Brett, Stephen J.

AU - Ip, Wai Kee Eddie

AU - Mila, Joan

AU - Peters, Mark J.

AU - Saevarsdottir, Saedis

AU - Van Till, J. W.Oliver

AU - Hinds, Charles J.

AU - McBryde, Emma S.

PY - 2008/8/15

Y1 - 2008/8/15

N2 - 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 μg/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.

AB - 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 μg/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.

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