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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| Veröffentlicht in: | Clinical infectious diseases 2009-11, Vol.49 (10), p.1486-1491 |
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| creator | 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. |
| description | 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, |
| doi_str_mv | 10.1086/644619 |
| format | Article |
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Lewis ; Barnes, Rosemary A. ; Griffin, George ; Lindsay, Jodi A. ; Harrison, Thomas S.</creator><creatorcontrib>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.</creatorcontrib><description>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.</description><identifier>ISSN: 1058-4838</identifier><identifier>EISSN: 1537-6591</identifier><identifier>DOI: 10.1086/644619</identifier><identifier>PMID: 19827955</identifier><identifier>CODEN: CIDIEL</identifier><language>eng</language><publisher>Oxford: The University of Chicago Press</publisher><subject>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</subject><ispartof>Clinical infectious diseases, 2009-11, Vol.49 (10), p.1486-1491</ispartof><rights>2009 Infectious Diseases Society of America</rights><rights>2009 by the Infectious Diseases Society of America 2009</rights><rights>2009 INIST-CNRS</rights><rights>Copyright University of Chicago, acting through its Press Nov 15, 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c485t-51ff7f84c5d902839aa6c0fd47e0e1a78f29d047c6b61150f72f1663c396c5e73</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/27799377$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/27799377$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,776,780,799,27901,27902,57992,58225</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22121870$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19827955$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lambourne, Jonathan</creatorcontrib><creatorcontrib>Agranoff, Dan</creatorcontrib><creatorcontrib>Herbrecht, Raoul</creatorcontrib><creatorcontrib>Troke, Peter F.</creatorcontrib><creatorcontrib>Buchbinder, Aby</creatorcontrib><creatorcontrib>Willis, Fenella</creatorcontrib><creatorcontrib>Letscher-Bru, Valérie</creatorcontrib><creatorcontrib>Agrawal, Samir</creatorcontrib><creatorcontrib>Doffman, Sarah</creatorcontrib><creatorcontrib>Johnson, Elizabeth</creatorcontrib><creatorcontrib>White, P. Lewis</creatorcontrib><creatorcontrib>Barnes, Rosemary A.</creatorcontrib><creatorcontrib>Griffin, George</creatorcontrib><creatorcontrib>Lindsay, Jodi A.</creatorcontrib><creatorcontrib>Harrison, Thomas S.</creatorcontrib><title>Association of Mannose-Binding Lectin Deficiency with Acute Invasive Aspergillosis in Immunocompromised Patients</title><title>Clinical infectious diseases</title><addtitle>Clinical Infectious Diseases</addtitle><addtitle>Clinical Infectious Diseases</addtitle><description>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.</description><subject>Adult</subject><subject>Animal models</subject><subject>Animals</subject><subject>Antifungals</subject><subject>ARTICLES AND COMMENTARIES</subject><subject>Aspergillosis</subject><subject>Aspergillosis - epidemiology</subject><subject>Aspergillosis - immunology</subject><subject>Aspergillus</subject><subject>Biological and medical sciences</subject><subject>Disease Susceptibility</subject><subject>Drug therapy</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Enzymes</subject><subject>Female</subject><subject>Fungi</subject><subject>Genes</subject><subject>Glycoproteins</subject><subject>Human mycoses</subject><subject>Humans</subject><subject>Immunocompromised Host</subject><subject>Immunocompromised hosts</subject><subject>Immunocompromised populations</subject><subject>Immunodeficiencies</subject><subject>Immunodeficiencies. Immunoglobulinopathies</subject><subject>Immunopathology</subject><subject>Infection</subject><subject>Infections</subject><subject>Infectious diseases</subject><subject>Lectins</subject><subject>Male</subject><subject>Mannose-binding lectin</subject><subject>Mannose-Binding Lectin - blood</subject><subject>Mannose-Binding Lectin - deficiency</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Miscellaneous mycoses</subject><subject>Mortality</subject><subject>Mycoses</subject><subject>Neutrophils</subject><subject>Pathogens</subject><subject>Pattern recognition</subject><subject>Prevalence</subject><subject>Respiratory diseases</subject><subject>Risk factors</subject><subject>Studies</subject><issn>1058-4838</issn><issn>1537-6591</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqN0V1rFDEUBuBBFFur_gNlFNSr0WTyfbldP7qyVS8UZG9CmklqtjPJmjNT7b83OksLguBVAufhnJO8VfUQo5cYSf6KU8qxulUdYkZEw5nCt8sdMdlQSeRBdQ9gixDGErG71QFWshWKscNqtwBINpgxpFgnX5-aGBO45jjELsTzeu3sGGL92vlgg4v2qv4Rxm_1wk6jq1fx0kC4dPUCdi6fh75PEKAufjUMU0w2DbuchgCuqz-VES6OcL-6400P7sH-PKq-vH3zeXnSrD--Wy0X68ZSycaGYe-Fl9SyTqFWEmUMt8h3VDjksBHSt6pDVFh-xjFmyIvWY86JJYpb5gQ5ql7MfcsG3ycHoy57WNf3Jro0gRaMMoqw-A9JiKIIMVbk07_kNk05lmfoFivFMcKqoOczsjkBZOf1LofB5CuNkf6dlZ6zKvDxvtt0Nrjuhu3DKeDZHhiwpvfZRBvg2rUtbrEUqLgns0vT7t_DHs1mC2PKNz2EUIr8-YRmrgcY3c_ruskXmgsimD75utGb9v2xXH441RvyC9Kivaw</recordid><startdate>20091115</startdate><enddate>20091115</enddate><creator>Lambourne, Jonathan</creator><creator>Agranoff, Dan</creator><creator>Herbrecht, Raoul</creator><creator>Troke, Peter F.</creator><creator>Buchbinder, Aby</creator><creator>Willis, Fenella</creator><creator>Letscher-Bru, Valérie</creator><creator>Agrawal, Samir</creator><creator>Doffman, Sarah</creator><creator>Johnson, Elizabeth</creator><creator>White, P. Lewis</creator><creator>Barnes, Rosemary A.</creator><creator>Griffin, George</creator><creator>Lindsay, Jodi A.</creator><creator>Harrison, Thomas S.</creator><general>The University of Chicago Press</general><general>University of Chicago Press</general><general>Oxford University Press</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7T2</scope><scope>7T7</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope><scope>7T5</scope></search><sort><creationdate>20091115</creationdate><title>Association of Mannose-Binding Lectin Deficiency with Acute Invasive Aspergillosis in Immunocompromised Patients</title><author>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.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c485t-51ff7f84c5d902839aa6c0fd47e0e1a78f29d047c6b61150f72f1663c396c5e73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adult</topic><topic>Animal models</topic><topic>Animals</topic><topic>Antifungals</topic><topic>ARTICLES AND COMMENTARIES</topic><topic>Aspergillosis</topic><topic>Aspergillosis - epidemiology</topic><topic>Aspergillosis - immunology</topic><topic>Aspergillus</topic><topic>Biological and medical sciences</topic><topic>Disease Susceptibility</topic><topic>Drug therapy</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Enzymes</topic><topic>Female</topic><topic>Fungi</topic><topic>Genes</topic><topic>Glycoproteins</topic><topic>Human mycoses</topic><topic>Humans</topic><topic>Immunocompromised Host</topic><topic>Immunocompromised hosts</topic><topic>Immunocompromised populations</topic><topic>Immunodeficiencies</topic><topic>Immunodeficiencies. Immunoglobulinopathies</topic><topic>Immunopathology</topic><topic>Infection</topic><topic>Infections</topic><topic>Infectious diseases</topic><topic>Lectins</topic><topic>Male</topic><topic>Mannose-binding lectin</topic><topic>Mannose-Binding Lectin - blood</topic><topic>Mannose-Binding Lectin - deficiency</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Miscellaneous mycoses</topic><topic>Mortality</topic><topic>Mycoses</topic><topic>Neutrophils</topic><topic>Pathogens</topic><topic>Pattern recognition</topic><topic>Prevalence</topic><topic>Respiratory diseases</topic><topic>Risk factors</topic><topic>Studies</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lambourne, Jonathan</creatorcontrib><creatorcontrib>Agranoff, Dan</creatorcontrib><creatorcontrib>Herbrecht, Raoul</creatorcontrib><creatorcontrib>Troke, Peter F.</creatorcontrib><creatorcontrib>Buchbinder, Aby</creatorcontrib><creatorcontrib>Willis, Fenella</creatorcontrib><creatorcontrib>Letscher-Bru, Valérie</creatorcontrib><creatorcontrib>Agrawal, Samir</creatorcontrib><creatorcontrib>Doffman, Sarah</creatorcontrib><creatorcontrib>Johnson, Elizabeth</creatorcontrib><creatorcontrib>White, P. Lewis</creatorcontrib><creatorcontrib>Barnes, Rosemary A.</creatorcontrib><creatorcontrib>Griffin, George</creatorcontrib><creatorcontrib>Lindsay, Jodi A.</creatorcontrib><creatorcontrib>Harrison, Thomas S.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><jtitle>Clinical infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lambourne, Jonathan</au><au>Agranoff, Dan</au><au>Herbrecht, Raoul</au><au>Troke, Peter F.</au><au>Buchbinder, Aby</au><au>Willis, Fenella</au><au>Letscher-Bru, Valérie</au><au>Agrawal, Samir</au><au>Doffman, Sarah</au><au>Johnson, Elizabeth</au><au>White, P. Lewis</au><au>Barnes, Rosemary A.</au><au>Griffin, George</au><au>Lindsay, Jodi A.</au><au>Harrison, Thomas S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association of Mannose-Binding Lectin Deficiency with Acute Invasive Aspergillosis in Immunocompromised Patients</atitle><jtitle>Clinical infectious diseases</jtitle><stitle>Clinical Infectious Diseases</stitle><addtitle>Clinical Infectious Diseases</addtitle><date>2009-11-15</date><risdate>2009</risdate><volume>49</volume><issue>10</issue><spage>1486</spage><epage>1491</epage><pages>1486-1491</pages><issn>1058-4838</issn><eissn>1537-6591</eissn><coden>CIDIEL</coden><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.</abstract><cop>Oxford</cop><pub>The University of Chicago Press</pub><pmid>19827955</pmid><doi>10.1086/644619</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 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 |
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