Serological proteome analysis to identify systemic candidiasis patients in the intensive care unit: Analytical, diagnostic and prognostic validation of anti-Candida enolase antibodies on quantitative clinical platforms.

Systemic candidiasis (SC) is associated with high morbidity and mortality, because it generally affects patients with severe underlying diseases and its diagnosis is difficult and often delayed, resulting in delayed therapy. We used serological proteome analysis to screen serum anti-Candida IgG antibody-reactivity profiles in 24 patients under intensive care, 12 of which had confirmed SC (fungal cultures), and in 12 healthy subjects. A total of 15 immunogenic proteins from Candida albicans protoplast lysates were differentially immunorecognized by serum IgG antibodies from SC patients compared to controls. Two-way hierarchical clustering and principal-component analyses of these antibody-reactivity patterns accurately differentiated SC patients from controls. Anti-Eno1p IgG antibodies were found to be present at high abundance in SC patients and be an important molecular fingerprint in serum for SC diagnosis. Differential anti-Eno1p IgG antibody reactivity was further validated by a tag capture ELISA and a Western blot assay in 45 SC patients and 118 non-SC subjects. Both quantitative assays provided comparable analytical, diagnostic and prognostic performances, and verified initial proteomic-profiling results. If confirmed in prospective cohort studies, these anti-Eno1p IgG antibodies might be useful for SC diagnosis. However, these, at least as measured by these clinical platforms, appear to have limited prognostic value in SC patients.