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 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.
Lambourne
Jonathan
J
Dept of Infection, Division of Cellular and Molecular Medicine, St George's University, Cranmer Terrace, London SW17 0RE, England. jlambourne@sgul.ac.uk
Agranoff
Dan
D
Herbrecht
Raoul
R
Troke
Peter F
PF
Buchbinder
Aby
A
Willis
Fenella
F
Letscher-Bru
Valérie
V
Agrawal
Samir
S
Doffman
Sarah
S
Johnson
Elizabeth
E
White
P Lewis
PL
Barnes
Rosemary A
RA
Griffin
George
G
Lindsay
Jodi A
JA
Harrison
Thomas S
TS
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
D037601:Mannose-Binding Lectin