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

2.50
Hdl Handle:
http://hdl.handle.net/2336/42333
Title:
Low serum mannose-binding lectin level increases the risk of death due to pneumococcal infection.
Authors:
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; Ip, W K Eddie; Mila, Joan; Peters, Mark J; Saevarsdottir, Saedis; van Till, J W Oliver; Hinds, Charles J; McBryde, Emma S
Citation:
Clin. Infect. Dis. 2008, 47(4):510-6
Issue Date:
15-Aug-2008
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.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field
Additional Links:
http://www.journals.uchicago.edu/doi/abs/10.1086/590006

Full metadata record

DC FieldValue Language
dc.contributor.authorEisen, Damon P-
dc.contributor.authorDean, Melinda M-
dc.contributor.authorBoermeester, Marja A-
dc.contributor.authorFidler, Katy J-
dc.contributor.authorGordon, Anthony C-
dc.contributor.authorKronborg, Gitte-
dc.contributor.authorKun, Jürgen F J-
dc.contributor.authorLau, Yu Lung-
dc.contributor.authorPayeras, Antonis-
dc.contributor.authorValdimarsson, Helgi-
dc.contributor.authorBrett, Stephen J-
dc.contributor.authorIp, W K Eddie-
dc.contributor.authorMila, Joan-
dc.contributor.authorPeters, Mark J-
dc.contributor.authorSaevarsdottir, Saedis-
dc.contributor.authorvan Till, J W Oliver-
dc.contributor.authorHinds, Charles J-
dc.contributor.authorMcBryde, Emma S-
dc.date.accessioned2008-12-15T09:10:02Z-
dc.date.available2008-12-15T09:10:02Z-
dc.date.issued2008-08-15-
dc.date.submitted2008-12-15-
dc.identifier.citationClin. Infect. Dis. 2008, 47(4):510-6en
dc.identifier.issn1058-4838-
dc.identifier.pmid18611155-
dc.identifier.doi10.1086/590006-
dc.identifier.urihttp://hdl.handle.net/2336/42333-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractBACKGROUND: 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.en
dc.language.isoenen
dc.publisherThe University of Chicago Pressen
dc.relation.urlhttp://www.journals.uchicago.edu/doi/abs/10.1086/590006en
dc.subject.meshAPACHEen
dc.subject.meshAdulten
dc.subject.meshBacteremiaen
dc.subject.meshChilden
dc.subject.meshChild, Preschoolen
dc.subject.meshGenotypeen
dc.subject.meshHumansen
dc.subject.meshMannose-Binding Lectinen
dc.subject.meshPneumococcal Infectionsen
dc.subject.meshPredictive Value of Testsen
dc.subject.meshROC Curveen
dc.subject.meshRisk Factorsen
dc.titleLow serum mannose-binding lectin level increases the risk of death due to pneumococcal infection.en
dc.typeArticleen
dc.identifier.eissn1537-6591-
dc.contributor.departmentCentre for Clinical Research Excellence in Infectious Diseases, Victorian Infectious Diseases Service, Royal Melbourne Hospital, Parkville, Victoria, Australia. damon.eisen@mh.org.auen
dc.identifier.journalClinical infectious diseases : an official publication of the Infectious Diseases Society of Americaen

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