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; 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

doi:10.1086/590006

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, 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

Department of Clinical Medicine

150 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 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.

Original language	English
Journal	Clinical Infectious Diseases
Volume	47
Issue number	4
Pages (from-to)	510-6
Number of pages	6
ISSN	1058-4838
DOIs	https://doi.org/10.1086/590006 https://doi.org/10.1086/590006
Publication status	Published - 2008

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Eisen, D. P., Dean, M. M., Boermeester, M. A., Fidler, K. J., Gordon, A. C., Kronborg, G., Kun, J. F. J., Lau, Y. L., Payeras, A., Valdimarsson, H., Brett, S. J., Ip, W. K. E., Mila, J., Peters, M. J., Saevarsdottir, S., van Till, J. W. O., Hinds, C. J., & McBryde, E. S. (2008). Low serum mannose-binding lectin level increases the risk of death due to pneumococcal infection. Clinical Infectious Diseases, 47(4), 510-6. https://doi.org/10.1086/590006, https://doi.org/10.1086/590006

Eisen, DP, Dean, MM, Boermeester, MA, Fidler, KJ, Gordon, AC, Kronborg, G, Kun, JFJ, Lau, YL, 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. 510-6. https://doi.org/10.1086/590006, https://doi.org/10.1086/590006

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title = "Low serum mannose-binding lectin level increases the risk of death due to pneumococcal infection.",

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.",

author = "Eisen, {Damon P} and Dean, {Melinda M} and Boermeester, {Marja A} and Fidler, {Katy J} and Gordon, {Anthony C} and Gitte Kronborg and Kun, {J{\"u}rgen F J} and Lau, {Yu Lung} and Antonis Payeras and Helgi Valdimarsson and Brett, {Stephen J} and Ip, {W K Eddie} and Joan Mila and Peters, {Mark J} and Saedis Saevarsdottir and {van Till}, {J W Oliver} and Hinds, {Charles J} and McBryde, {Emma S}",

year = "2008",

doi = "10.1086/590006",

language = "English",

volume = "47",

pages = "510--6",

journal = "Clinical Infectious Diseases",

issn = "1058-4838",

publisher = "Oxford University Press",

number = "4",

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TY - JOUR

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 - Lau, Yu Lung

AU - Payeras, Antonis

AU - Valdimarsson, Helgi

AU - Brett, Stephen J

AU - Ip, W K 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

Y1 - 2008

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 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.

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 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.

U2 - 10.1086/590006

DO - 10.1086/590006

M3 - Journal article

C2 - 18611155

SN - 1058-4838

VL - 47

SP - 510

EP - 516

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

IS - 4

ER -

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

Abstract

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