Journal Article

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

Jonathan Lambourne, Dan Agranoff, Raoul Herbrecht, Peter F. Troke, Aby Buchbinder, Fenella Willis, Valérie Letscher-Bru, Samir Agrawal, Sarah Doffman, Elizabeth Johnson, P. Lewis White, Rosemary A. Barnes, George Griffin, Jodi A. Lindsay and Thomas S. Harrison

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 49, issue 10, pages 1486-1491
Published in print November 2009 | ISSN: 1058-4838
Published online November 2009 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/644619
Association of Mannose-Binding Lectin Deficiency with Acute Invasive Aspergillosis in Immunocompromised Patients

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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.

Journal Article.  4239 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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