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

Background. Invasive aspergillosisis 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 receptorthat activates complement, is a susceptibility factor. MBL deficiencyoccurs in 20%-30% of the population. We hypothesized that MBL deficiencymay be a susceptibility factor for invasive aspergillosisin humans. Methods. Serum MBL concentrations were measured by enzyme-linked immunosorbent assay in 65 patients with proven or probable acute invasive aspergillosisand 78 febrile immunocompromised control subjects. MBL concentrations and the frequency of MBL deficiencywere compared. Results. The median serum MBL level was significantly lower in patients with aspergillosisthan 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 aspergillosisthan control subjects (62% vs 32%; P<.001). Frequency of MBL deficiencywas similar among patients with aspergillosisirrespective of response to antifungal therapy (P=.10). Conclusions. This study is the first, to our knowledge, to show an association between MBL deficiencyand acute invasive aspergillosisin humans. Further study is required to investigate the causal nature of this association and to define whether diagnosis of MBL deficiencymay identify immunocompromised patients at increased risk of invasive aspergillosis.