Immunoglobulin G Responses to a Panel of Candida albicans Antigens as Accurate and Early Markers for the Presence of Systemic Candidiasis

Abstract

Despite shortcomings, cultures of blood and sterile sites remain the "gold standard" for diagnosing systemic candidiasis. Alternative diagnostic markers, including antibody detection, have been developed, but none are widely accepted. In this study, we used an enzyme-linked immunosorbent assay to measure serum antibody responses against 15 recombinant Candida albicans antigens among 60 patients with systemic candidiasis due to various Candida spp. and 24 uninfected controls. Mean immunoglobulin G (IgG) responses against all 15 antigens were significantly higher among patients with systemic candidiasis than among controls, whereas IgM responses were higher against only seven antigens. Using discriminant analysis that included IgG responses against the 15 antigens, we derived a mathematical prediction model that identified patients with systemic candidiasis with an error rate of 3.7%, a sensitivity of 96.6%, and a specificity of 95.6%. Furthermore, a prediction model using a subset of four antigens (SET1, ENO1, PGK1-2, and MUC1-2) identified through backward elimination and canonical correlation analyses performed as accurately as the full panel. Using the simplified model, we predicted systemic candidiasis in a separate test sample of 32 patients and controls with 100% sensitivity and 87.5% specificity. We also demonstrated that IgG titers against each of the four antigens included in the prediction model were significantly higher in convalescent-phase sera than in paired acutephase sera. Taken together, our findings suggest that IgG responses against a panel of candidal antigens might represent an accurate and early marker of systemic candidiasis, a hypothesis that should be tested in future trials.

Synthetic glycopeptide vaccines combining β-mannan and peptide epitopes induce protection against candidiasis

“…albicans carrier proteins were selected from previously identified cell wall proteins that are expressed during pathogenesis of human disseminated candidiasis (22,23). The selected six candidate carriers were fructose-bisphosphate aldolase (Fba); methyltetrahydropteroyltriglutamate (Met6); hyphal wall protein-1 (Hwp1); enolase (Enol); glyceraldehyde-3-phosphate dehydrogenase (Gap1); and phosphoglycerate kinase (Pgk1).…”

“…Six cell wall proteins were selected as possible carriers on the basis of their known expression during pathogenesis of human candidiasis a cell wall location (22,23) and included: hyphal wall protein-1 (Hwp1); enolase (Enol); phosphoglycerate kinase (Pgk1); glyceraldehyde-3-phosphate dehydrogenase (Gap1); fructose-bisphosphate aldolase (Fba); and methyltetrahydropteroyltriglutamate (Met6). By application of an epitopefinding algorithm (www.genscript.com/cgibin/tools/antigenic prediction.pl), we selected the following 14-mer peptides for synthesis, all of which are located near the N terminus of each protein group: Hwp1, QGETEEALIQKRSY; Eno1, DSRGNPTVEVDFTT; Pgk1, VPLDGKTITNNQRI; Gap1, NRSPSTGEQKSSGI; Fba, YGK-DVKDLFDYAQE; and, Met6, PRIGGQRELKKITE.…”

Vaccine and Monoclonal Antibody That Enhance Mouse Resistance to Candidiasis

“…C. albicans carrier peptides were selected from previously identified cell wall proteins that are expressed during the pathogenesis of human disseminated candidiasis (11,46). We selected six candidate carriers, each of which was comprised of 14 amino acids located near the N terminus of their respective complete protein, presumed to be located in the cell wall of the fungus (46).…”

Antibodies against Glucan, Chitin, and Saccharomyces cerevisiae Mannan as New Biomarkers of Candida albicans Infection That Complement Tests Based on C. albicans Mannan

“…Thus, the future of serological diagnosis appears to be based on the use of multiple antigens and currently available technologies (7). In the case of fungal cell wall carbohydrates, the ubiquitous distribution of chitin and glucans suggests that ALCA and FIG.…”