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Submitted on August 1, 2005
Microbiology II, Complutense University of Madrid, Madrid 28040
Corresponding Author: conchagil{at}farm.ucm.es
In an effort to bring novel diagnostic and prognostic biomarkers or, even, potential targets for vaccine design for systemic candidiasis (SC) into the open, a systematic proteomic approach, coupled with bioinformatic analysis, was used to decode the serological response to Candida wall immunome in SC patients. Serum levels of IgG antibodies against Candida wall-associated proteins –proteins secreted from protoplasts in active wall regeneration, separated by two-dimensional gel electrophoresis, and identified by mass spectrometry– were measured in 45 SC patients, 57 non-SC patients, and 61 healthy subjects by Western-blotting. Two-way hierarchical clustering and principal-component analysis of their anti-Candida wall antibody-expression patterns discriminated SC patients from controls, and highlighted the heterogeneity of their expression profiles. Multivariate logistic-regression models demonstrated that high levels of antibodies against glucan 1,3-beta-glucosidase (Bgl2p) and the anti-wall phosphoglycerate kinase antibody seropositivity were the only independent predictors of SC. Receiver-operating-characteristic curve analysis revealed no difference between their combined evaluation and measurement of anti-Bgl2p antibodies alone. In a logistic-regression model adjusted for known prognostic factors for mortality, SC patients with high anti-Bgl2p antibody levels or a positive anti-wall enolase antibody status, which correlated with each other, had a reduced two-month risk of death. After controlling for each other, only the seropositivity for anti-wall enolase antibodies was an independent predictor of a lower risk of fatality, supporting that these mediated the protective effect. No association between anti-cytoplasmic enolase antibody levels and outcomes was established, suggesting a specific mechanism of enolase processing during wall biogenesis. We conclude that anti-Bgl2p antibodies are a novel accurate diagnostic biomarker for SC and that, at high levels, they may provide protection by modulating the anti-wall enolase antibody response. Furthermore, anti-wall enolase antibodies are a new prognostic indicator for SC and, confer protection against it. Bgl2p and wall-associated enolase could be valuable candidates for future vaccine development.
Revised on September 13, 2005
Accepted on September 28, 2005
Decoding serological response to Candida cell wall immunome into novel diagnostic, prognostic and therapeutic candidates for systemic candidiasis by proteomic and bioinformatic analyses
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