title: Association of mannose-binding lectin deficiency with acute invasive aspergillosis in immunocompromised patients.
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.
authors.affiliation: Dept of Infection, Division of Cellular and Molecular Medicine, St George's University, Cranmer Terrace, London SW17 0RE, England. jlambourne@sgul.ac.uk
authors.forename: Jonathan
authors.initials: J
authors.lastname: Lambourne
authors.forename: Dan
authors.initials: D
authors.lastname: Agranoff
authors.forename: Raoul
authors.initials: R
authors.lastname: Herbrecht
authors.forename: Peter F
authors.initials: PF
authors.lastname: Troke
authors.forename: Aby
authors.initials: A
authors.lastname: Buchbinder
authors.forename: Fenella
authors.initials: F
authors.lastname: Willis
authors.forename: Valérie
authors.initials: V
authors.lastname: Letscher-Bru
authors.forename: Samir
authors.initials: S
authors.lastname: Agrawal
authors.forename: Sarah
authors.initials: S
authors.lastname: Doffman
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Johnson
authors.forename: P Lewis
authors.initials: PL
authors.lastname: White
authors.forename: Rosemary A
authors.initials: RA
authors.lastname: Barnes
authors.forename: George
authors.initials: G
authors.lastname: Griffin
authors.forename: Jodi A
authors.initials: JA
authors.lastname: Lindsay
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Harrison
mesh_terms: D000328:Adult; D000818:Animals; D001228:Aspergillosis / Q000453:epidemiology* / Q000276:immunology*; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D008297:Male; D037601:Mannose-Binding Lectin / Q000097:blood / Q000172:deficiency*; D008875:Middle Aged; D015995:Prevalence
chemical_list: D037601:Mannose-Binding Lectin