Mannose-Binding Lectin Deficiency - a Risk Factor for Invasive Aspergillosis in Immunocompromised Patients
Invasive aspergillosis is a devastating infection with 30–40% mortality. Immune mechanisms involved in recognition and elimination of aspergillus are incompletely understood. Mannose-binding lectin (MBL) deficiency occurs in 10–15% of the population and has been identified as a susceptibility factor...
Saved in:
Published in | Blood Vol. 112; no. 11; p. 1465 |
---|---|
Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Elsevier Inc
16.11.2008
|
Online Access | Get full text |
Cover
Loading…
Abstract | Invasive aspergillosis is a devastating infection with 30–40% mortality. Immune mechanisms involved in recognition and elimination of aspergillus are incompletely understood. Mannose-binding lectin (MBL) deficiency occurs in 10–15% of the population and has been identified as a susceptibility factor in animal models of aspergillosis. We hypothesise there is an association between human MBL deficiency and invasive aspergillosis.
In this multi-centre case-control study, serum MBL concentrations were measured in 65 patients with probable or proven invasive aspergillosis (as defined by the 2002 EORTC/NIH-MSG criteria) and in 79 immunocompromised controls with fever not due to aspergillosis. MBL concentrations were measured using a commercially available, technically straightforward solid phase ELISA (Hycult Biotechnology, The Netherlands). Median MBL concentrations and the frequency of MBL deficiency were compared using the Mann-Whitney and Fisher's exact tests.
Cases and controls were well matched in terms of age, gender, ethnicity and cause of immunocompromise. The assay performed well with a mean coefficient of variation of 7%. Patients with invasive aspergillosis had significantly lower MBL concentrations and a greater frequency of MBL deficiency than controls (65% vs. 33%, p = 0.0002, MBL deficiency cut-off 500ng/ml). MBL deficiency was significantly more frequent in cases than in controls at all MBL concentrations ≤500ng/ml. This is the first study to identify a strong association between MBL deficiency and invasive aspergillosis in immunocompromised patients. Because MBL concentrations do not consistently change during acute infection we conclude that MBL deficiency predisposes to invasive aspergillosis. Routine measurement of MBL levels is within the capability of most diagnostic laboratories. These data suggest that replacement therapy with recombinant human MBL may be an opportunity to prevent or mitigate the poor outcome of invasive aspergillosis. |
---|---|
AbstractList | Invasive aspergillosis is a devastating infection with 30–40% mortality. Immune mechanisms involved in recognition and elimination of aspergillus are incompletely understood. Mannose-binding lectin (MBL) deficiency occurs in 10–15% of the population and has been identified as a susceptibility factor in animal models of aspergillosis. We hypothesise there is an association between human MBL deficiency and invasive aspergillosis.
In this multi-centre case-control study, serum MBL concentrations were measured in 65 patients with probable or proven invasive aspergillosis (as defined by the 2002 EORTC/NIH-MSG criteria) and in 79 immunocompromised controls with fever not due to aspergillosis. MBL concentrations were measured using a commercially available, technically straightforward solid phase ELISA (Hycult Biotechnology, The Netherlands). Median MBL concentrations and the frequency of MBL deficiency were compared using the Mann-Whitney and Fisher’s exact tests.
Cases and controls were well matched in terms of age, gender, ethnicity and cause of immunocompromise. The assay performed well with a mean coefficient of variation of 7%. Patients with invasive aspergillosis had significantly lower MBL concentrations and a greater frequency of MBL deficiency than controls (65% vs. 33%, p = 0.0002, MBL deficiency cut-off 500ng/ml). MBL deficiency was significantly more frequent in cases than in controls at all MBL concentrations ≤500ng/ml. This is the first study to identify a strong association between MBL deficiency and invasive aspergillosis in immunocompromised patients. Because MBL concentrations do not consistently change during acute infection we conclude that MBL deficiency predisposes to invasive aspergillosis. Routine measurement of MBL levels is within the capability of most diagnostic laboratories. These data suggest that replacement therapy with recombinant human MBL may be an opportunity to prevent or mitigate the poor outcome of invasive aspergillosis. |
Author | Herbrecht, Raoul Lindsay, Jodi Buchbinder, Aby Harrison, Thomas Agranoff, Dan Troke, Peter F Lambourne, Jonathan |
Author_xml | – sequence: 1 givenname: Jonathan surname: Lambourne fullname: Lambourne, Jonathan organization: Centre for Infection, Division of Cellular & Molecular Medicine, St George's University London, London, United Kingdom – sequence: 2 givenname: Dan surname: Agranoff fullname: Agranoff, Dan organization: Department of Infectious Diseases & Immunity, Imperial College London, London, United Kingdom – sequence: 3 givenname: Aby surname: Buchbinder fullname: Buchbinder, Aby organization: Enzon Pharmaceuticals Inc., Bridgewater, NJ, USA – sequence: 4 givenname: Peter F surname: Troke fullname: Troke, Peter F organization: Global Research & Development, Pfizer Inc. (Retired), Sandwich, United Kingdom – sequence: 5 givenname: Raoul surname: Herbrecht fullname: Herbrecht, Raoul organization: Oncology and Hematology, Hopital de Hautepierre, Strasbourg Cedex, France – sequence: 6 givenname: Jodi surname: Lindsay fullname: Lindsay, Jodi organization: Centre for Infection, Division of Cellular & Molecular Medicine, St George's University London, London, United Kingdom – sequence: 7 givenname: Thomas surname: Harrison fullname: Harrison, Thomas organization: Centre for Infection, Division of Cellular & Molecular Medicine, St George's University London, London, United Kingdom |
BookMark | eNqFkM1OAjEUhRuDiYA-g32Bwd7S-WGJKEqC0Rh12_SXFJmWtCMJb28Z3Lu45-YszsnJN0IDH7xB6BbIBKChd3IXgp58AdDsJ8CqspcLNISSNgUhlAzQkBBSFWxWwxUapbQlBNiUlkO0fRHeh2SKe-e18xu8NqpzHj8Y65QzXh1xgQV-d-kbL4XqQsQ238ofRHIHg-dpb-LG7XYhuYRzcNW2Pz6o0O5jaF0yGr-JLhd16RpdWrFL5ubvj9Hn8vFj8VysX59Wi_m6UECqshAzYCCVrEvQUFutGiln0ioJspSMKttUghrCalsRBmYKhggFjdC6qWjD2HSM6nOviiGlaCzfR9eKeORA-AkZ75HxE7Ls-YlWLzk5PydNnndwJvLUMzDaxYyF6-D-7fgFFkx6Vg |
ContentType | Journal Article |
Copyright | 2008 American Society of Hematology |
Copyright_xml | – notice: 2008 American Society of Hematology |
DBID | 6I. AAFTH AAYXX CITATION |
DOI | 10.1182/blood.V112.11.1465.1465 |
DatabaseName | ScienceDirect Open Access Titles Elsevier:ScienceDirect:Open Access CrossRef |
DatabaseTitle | CrossRef |
DatabaseTitleList | CrossRef |
DeliveryMethod | fulltext_linktorsrc |
Discipline | Medicine Chemistry Biology Anatomy & Physiology |
EISSN | 1528-0020 |
EndPage | 1465 |
ExternalDocumentID | 10_1182_blood_V112_11_1465_1465 S0006497119487612 |
GroupedDBID | --- -~X .55 1CY 23N 2WC 34G 39C 4.4 53G 5GY 5RE 5VS 6I. 6J9 9M8 AAEDW AAFTH AAXUO ABOCM ABVKL ACGFO ADBBV AENEX AFFNX AFOSN AHPSJ ALMA_UNASSIGNED_HOLDINGS BAWUL BTFSW C1A CS3 DIK DU5 E3Z EBS EJD EX3 F5P FDB FRP GS5 GX1 IH2 K-O KQ8 L7B LSO MJL N4W N9A OK1 P2P R.V RHF RHI ROL SJN THE TR2 TWZ W2D W8F WH7 WOQ WOW X7M YHG YKV ZA5 ZGI 0R~ AAYXX ADVLN AITUG AKRWK AMRAJ CITATION H13 |
ID | FETCH-LOGICAL-c1065-a9141bcb751d17fdc8bb9bfcb1b5b42cf86a2e047f6041e31e0ac18add8628443 |
IEDL.DBID | ABVKL |
ISSN | 0006-4971 |
IngestDate | Fri Dec 06 03:40:28 EST 2024 Fri Feb 23 02:42:55 EST 2024 |
IsDoiOpenAccess | true |
IsOpenAccess | true |
IsPeerReviewed | true |
IsScholarly | true |
Issue | 11 |
Language | English |
License | This article is made available under the Elsevier license. |
LinkModel | DirectLink |
MergedId | FETCHMERGED-LOGICAL-c1065-a9141bcb751d17fdc8bb9bfcb1b5b42cf86a2e047f6041e31e0ac18add8628443 |
OpenAccessLink | https://www.sciencedirect.com/science/article/pii/S0006497119487612 |
PageCount | 1 |
ParticipantIDs | crossref_primary_10_1182_blood_V112_11_1465_1465 elsevier_sciencedirect_doi_10_1182_blood_V112_11_1465_1465 |
PublicationCentury | 2000 |
PublicationDate | 2008-11-16 |
PublicationDateYYYYMMDD | 2008-11-16 |
PublicationDate_xml | – month: 11 year: 2008 text: 2008-11-16 day: 16 |
PublicationDecade | 2000 |
PublicationTitle | Blood |
PublicationYear | 2008 |
Publisher | Elsevier Inc |
Publisher_xml | – name: Elsevier Inc |
SSID | ssj0014325 |
Score | 1.9461305 |
Snippet | Invasive aspergillosis is a devastating infection with 30–40% mortality. Immune mechanisms involved in recognition and elimination of aspergillus are... |
SourceID | crossref elsevier |
SourceType | Aggregation Database Publisher |
StartPage | 1465 |
Title | Mannose-Binding Lectin Deficiency - a Risk Factor for Invasive Aspergillosis in Immunocompromised Patients |
URI | https://dx.doi.org/10.1182/blood.V112.11.1465.1465 |
Volume | 112 |
hasFullText | 1 |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1LT9wwEB7xUIELKksRryIfKm7p2lk7D267CysoD9GqIG6R7XVQeCSIABL_nhknQVSq1EMvlhNpksiejOezv5kB-JZYVBOrbcAdt4FU2EsRpgRaCptGRkVO04b-6Vl0eCF_XKmrGRh3sTBEq2xtf2PTvbVu7_Tb0ew_FAXF-OJymsYCYTj-0lRpeJ5ymaNqzw9Hl8cn74cJchA2hQwQPJNAS_NCz7rv2eHfL9HpwGuyGso3f1-kPiw8k8-w3HqMbNh81ArMuLIHq8MS0fL9K9tlnsPpN8d78GnU9RbHXSW3Hiyctgfoq3BDRZGr2gWjwoezsBMyeCXbd5RJgsIwWcA0-1XUt2ziS_Ew9GrZUfmiiefOhpRY_Lq4u6vqomYoeETxJRUR0x8rfJ-bsvMmU2v9BS4mB7_Hh0FbbiGwiAtVoFMhhbEmVmIq4nxqE2NSk1sjjDIytHkS6dBxGecRl8INhOPaigQNJKKiRMrBGsyVVenWgSVaGovPSy03MkIvwnJldJhblwsdxXwDeDe-2UOTVSPzaCQJMz8lGU0JXhMyUb7ZgL1uHrI_FCRD2_8v4c3_Ed6CJU8SIe5ftA1zT4_P7it6Ik9mp9W0HZg9_pm8AYjs29s |
link.rule.ids | 314,780,784,27569,27924,27925,45663 |
linkProvider | Elsevier |
linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV3fT9swED4hEIOXaSubBvvlh2lvWe3UdpK9td2qFlo0TYB4i2zXmbJBgggg8d_vzkmmTZrEAy-WE-mSyL6c77O_uwP4kDpUE2dcxD13kVTYyxCmREYKl2mrtDe0ob861vNTeXiuzjdg2sfCEK2ys_2tTQ_Wursz7EZzeFWWFOOLy2mWCITh-EtTpeEt9AY0KvvWeHJ2tPxzmCBHcVvIAMEzCXQ0L_Ssh4Ed_ukMnQ68JquhQvP_ReqvhWf2DJ52HiMbtx_1HDZ8NYC9cYVo-fKefWSBwxk2xwewPel7O9O-ktsAnqy6A_Q9-ElFkevGR5MyhLOwJRm8in3xlEmCwjBZxAz7Xja_2CyU4mHo1bJFdWeI587GlFj8R3lxUTdlw1BwQfElNRHTr2t8n1-zb22m1uYFnM6-nkznUVduIXKIC1VkMiGFdTZRYi2SYu1SazNbOCussjJ2RapN7LlMCs2l8CPhuXEiRQOJqCiVcvQSNqu68q-ApUZah8_LHLdSoxfhuLImLpwvhNEJ3wfej29-1WbVyAMaSeM8TElOU4LXhExUaPbhcz8P-T8KkqPtf0j44DHC72FnfrJa5svF8dFr2A2EEeIB6jeweXN969-iV3Jj33Va9xu7I93L |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Mannose-Binding+Lectin+Deficiency+-+a+Risk+Factor+for+Invasive+Aspergillosis+in+Immunocompromised+Patients&rft.jtitle=Blood&rft.au=Lambourne%2C+Jonathan&rft.au=Agranoff%2C+Dan&rft.au=Buchbinder%2C+Aby&rft.au=Troke%2C+Peter+F&rft.date=2008-11-16&rft.pub=Elsevier+Inc&rft.issn=0006-4971&rft.eissn=1528-0020&rft.volume=112&rft.issue=11&rft.spage=1465&rft.epage=1465&rft_id=info:doi/10.1182%2Fblood.V112.11.1465.1465&rft.externalDocID=S0006497119487612 |
thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0006-4971&client=summon |
thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0006-4971&client=summon |
thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0006-4971&client=summon |