Association of Mannose-Binding Lectin Deficiency with Acute Invasive Aspergillosis in Immunocompromised Patients

Background. Invasive aspergillosis is a devastating infection with attributable mortality of 40% despite antifungal therapy. In animal models of aspergillosis, deficiency of mannose-binding lectin (MBL), a pattern recognition receptor that activates complement, is a susceptibility factor. MBL defici...

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Published inClinical infectious diseases Vol. 49; no. 10; pp. 1486 - 1491
Main Authors Lambourne, Jonathan, Agranoff, Dan, Herbrecht, Raoul, Troke, Peter F., Buchbinder, Aby, Willis, Fenella, Letscher-Bru, Valérie, Agrawal, Samir, Doffman, Sarah, Johnson, Elizabeth, White, P. Lewis, Barnes, Rosemary A., Griffin, George, Lindsay, Jodi A., Harrison, Thomas S.
Format Journal Article
LanguageEnglish
Published Oxford The University of Chicago Press 15.11.2009
University of Chicago Press
Oxford University Press
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Abstract Background. Invasive aspergillosis is a devastating infection with attributable mortality of 40% despite antifungal therapy. In animal models of aspergillosis, deficiency of mannose-binding lectin (MBL), a pattern recognition receptor that activates complement, is a susceptibility factor. MBL deficiency occurs in 20%-30% of the population. We hypothesized that MBL deficiency may be a susceptibility factor for invasive aspergillosis in humans. Methods. Serum MBL concentrations were measured by enzyme-linked immunosorbent assay in 65 patients with proven or probable acute invasive aspergillosis and 78 febrile immunocompromised control subjects. MBL concentrations and the frequency of MBL deficiency were compared. Results. The median serum MBL level was significantly lower in patients with aspergillosis than in control subjects (281 ng/mL vs 835 ng/mL; P=.007). MBL deficiency (MBL concentration, <500 ng/mL) was significantly more common in patients with aspergillosis than control subjects (62% vs 32%; P<.001). Frequency of MBL deficiency was similar among patients with aspergillosis irrespective of response to antifungal therapy (P=.10). Conclusions. This study is the first, to our knowledge, to show an association between MBL deficiency and acute invasive aspergillosis in humans. Further study is required to investigate the causal nature of this association and to define whether diagnosis of MBL deficiency may identify immunocompromised patients at increased risk of invasive aspergillosis.
AbstractList BACKGROUNDInvasive aspergillosis is a devastating infection with attributable mortality of 40% despite antifungal therapy. In animal models of aspergillosis, deficiency of mannose-binding lectin (MBL), a pattern recognition receptor that activates complement, is a susceptibility factor. MBL deficiency occurs in 20%-30% of the population. We hypothesized that MBL deficiency may be a susceptibility factor for invasive aspergillosis in humans.METHODSSerum MBL concentrations were measured by enzyme-linked immunosorbent assay in 65 patients with proven or probable acute invasive aspergillosis and 78 febrile immunocompromised control subjects. MBL concentrations and the frequency of MBL deficiency were compared.RESULTSThe median serum MBL level was significantly lower in patients with aspergillosis than in control subjects (281 ng/mL vs 835 ng/mL; P = .007). MBL deficiency (MBL concentration, <500 ng/mL) was significantly more common in patients with aspergillosis than control subjects (62% vs 32%; P < .001). Frequency of MBL deficiency was similar among patients with aspergillosis irrespective of response to antifungal therapy (P = .10).CONCLUSIONSThis study is the first, to our knowledge, to show an association between MBL deficiency and acute invasive aspergillosis in humans. Further study is required to investigate the causal nature of this association and to define whether diagnosis of MBL deficiency may identify immunocompromised patients at increased risk of invasive aspergillosis.
Background. Invasive aspergillosis is a devastating infection with attributable mortality of 40% despite antifungal therapy. In animal models of aspergillosis, deficiency of mannose-binding lectin (MBL), a pattern recognition receptor that activates complement, is a susceptibility factor. MBL deficiency occurs in 20%-30% of the population. We hypothesized that MBL deficiency may be a susceptibility factor for invasive aspergillosis in humans. Methods. Serum MBL concentrations were measured by enzyme-linked immunosorbent assay in 65 patients with proven or probable acute invasive aspergillosis and 78 febrile immunocompromised control subjects. MBL concentrations and the frequency of MBL deficiency were compared. Results. The median serum MBL level was significantly lower in patients with aspergillosis than in control subjects (281 ng/mL vs 835 ng/mL; P=.007). MBL deficiency (MBL concentration, <500 ng/mL) was significantly more common in patients with aspergillosis than control subjects (62% vs 32%; P<.001). Frequency of MBL deficiency was similar among patients with aspergillosis irrespective of response to antifungal therapy (P=.10). Conclusions. This study is the first, to our knowledge, to show an association between MBL deficiency and acute invasive aspergillosis in humans. Further study is required to investigate the causal nature of this association and to define whether diagnosis of MBL deficiency may identify immunocompromised patients at increased risk of invasive aspergillosis.
Background. Invasive aspergillosis is a devastating infection with attributable mortality of 40% despite antifungal therapy. In animal models of aspergillosis, deficiency of mannose-binding lectin (MBL), a pattern recognition receptor that activates complement, is a susceptibility factor. MBL deficiency occurs in 20%–30% of the population. We hypothesized that MBL deficiency may be a susceptibility factor for invasive aspergillosis in humans. Methods. Serum MBL concentrations were measured by enzyme-linked immunosorbent assay in 65 patients with proven or probable acute invasive aspergillosis and 78 febrile immunocompromised control subjects. MBL concentrations and the frequency of MBL deficiency were compared. Results. The median serum MBL level was significantly lower in patients with aspergillosis than in control subjects (281 ng/mL vs 835 ng/mL; P = .007). MBL deficiency (MBL concentration, <500 ng/mL) was significantly more common in patients with aspergillosis than control subjects (62% vs 32%; P<.001). Frequency of MBL deficiency was similar among patients with aspergillosis irrespective of response to antifungal therapy (P = .10). Conclusions. This study is the first, to our knowledge, to show an association between MBL deficiency and acute invasive aspergillosis in humans. Further study is required to investigate the causal nature of this association and to define whether diagnosis of MBL deficiency may identify immunocompromised patients at increased risk of invasive aspergillosis.
Invasive aspergillosis is a devastating infection with attributable mortality of 40% despite antifungal therapy. In animal models of aspergillosis, deficiency of mannose-binding lectin (MBL), a pattern recognition receptor that activates complement, is a susceptibility factor. MBL deficiency occurs in 20%-30% of the population. We hypothesized that MBL deficiency may be a susceptibility factor for invasive aspergillosis in humans. Serum MBL concentrations were measured by enzyme-linked immunosorbent assay in 65 patients with proven or probable acute invasive aspergillosis and 78 febrile immunocompromised control subjects. MBL concentrations and the frequency of MBL deficiency were compared. The median serum MBL level was significantly lower in patients with aspergillosis than in control subjects (281 ng/mL vs 835 ng/mL; P = .007). MBL deficiency (MBL concentration, <500 ng/mL) was significantly more common in patients with aspergillosis than control subjects (62% vs 32%; P < .001). Frequency of MBL deficiency was similar among patients with aspergillosis irrespective of response to antifungal therapy (P = .10). This study is the first, to our knowledge, to show an association between MBL deficiency and acute invasive aspergillosis in humans. Further study is required to investigate the causal nature of this association and to define whether diagnosis of MBL deficiency may identify immunocompromised patients at increased risk of invasive aspergillosis.
Invasive aspergillosis is a devastating infection with attributable mortality of 40% despite antifungal therapy. In animal models of aspergillosis, deficiency of mannose-binding lectin (MBL), a pattern recognition receptor that activates complement, is a susceptibility factor. MBL deficiency occurs in 20%-30% of the population. We hypothesized that MBL deficiency may be a susceptibility factor for invasive aspergillosis in humans. Serum MBL concentrations were measured by enzyme-linked immunosorbent assay in 65 patients with proven or probable acute invasive aspergillosis and 78 febrile immunocompromised control subjects. MBL concentrations and the frequency of MBL deficiency were compared. The median serum MBL level was significantly lower in patients with aspergillosis than in control subjects (281 ng/mL vs 835 ng/mL; P = .007). MBL deficiency (MBL concentration, <500 ng/mL) was significantly more common in patients with aspergillosis than control subjects (62% vs 32%; P < .001). Frequency of MBL deficiency was similar among patients with aspergillosis irrespective of response to antifungal therapy (P = .10 ). This study is the first, to our knowledge, to show an association between MBL deficiency and acute invasive aspergillosis in humans. Further study is required to investigate the causal nature of this association and to define whether diagnosis of MBL deficiency may identify immunocompromised patients at increased risk of invasive aspergillosis.
Author Herbrecht, Raoul
Buchbinder, Aby
White, P. Lewis
Griffin, George
Doffman, Sarah
Barnes, Rosemary A.
Lambourne, Jonathan
Agrawal, Samir
Lindsay, Jodi A.
Johnson, Elizabeth
Troke, Peter F.
Letscher-Bru, Valérie
Harrison, Thomas S.
Willis, Fenella
Agranoff, Dan
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Issue 10
Keywords Infection
Human
Immunopathology
Lectin
Mycosis
Acute
Deficiency
Aspergillosis
Mannose
Immune deficiency
Language English
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References 19827954 - Clin Infect Dis. 2009 Nov 15;49(10):1492-5
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Snippet Background. Invasive aspergillosis is a devastating infection with attributable mortality of 40% despite antifungal therapy. In animal models of aspergillosis,...
Background. Invasive aspergillosis is a devastating infection with attributable mortality of 40% despite antifungal therapy. In animal models of aspergillosis,...
Invasive aspergillosis is a devastating infection with attributable mortality of 40% despite antifungal therapy. In animal models of aspergillosis, deficiency...
BACKGROUNDInvasive aspergillosis is a devastating infection with attributable mortality of 40% despite antifungal therapy. In animal models of aspergillosis,...
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SubjectTerms Adult
Animal models
Animals
Antifungals
ARTICLES AND COMMENTARIES
Aspergillosis
Aspergillosis - epidemiology
Aspergillosis - immunology
Aspergillus
Biological and medical sciences
Disease Susceptibility
Drug therapy
Enzyme-linked immunosorbent assay
Enzymes
Female
Fungi
Genes
Glycoproteins
Human mycoses
Humans
Immunocompromised Host
Immunocompromised hosts
Immunocompromised populations
Immunodeficiencies
Immunodeficiencies. Immunoglobulinopathies
Immunopathology
Infection
Infections
Infectious diseases
Lectins
Male
Mannose-binding lectin
Mannose-Binding Lectin - blood
Mannose-Binding Lectin - deficiency
Medical sciences
Middle Aged
Miscellaneous mycoses
Mortality
Mycoses
Neutrophils
Pathogens
Pattern recognition
Prevalence
Respiratory diseases
Risk factors
Studies
Title Association of Mannose-Binding Lectin Deficiency with Acute Invasive Aspergillosis in Immunocompromised Patients
URI https://api.istex.fr/ark:/67375/HXZ-Z2JB8CNM-Z/fulltext.pdf
https://www.jstor.org/stable/27799377
https://www.ncbi.nlm.nih.gov/pubmed/19827955
https://www.proquest.com/docview/219961019
https://search.proquest.com/docview/733940055
https://search.proquest.com/docview/754540177
Volume 49
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