In this study, we have developed a C. albicans cell surface protein microarray and profiled host humoral responses during conmmensal colonization and during the progression of candidemia. Thirteen novel serodiagnostic antigens were identified for differentiating acute candidemia from commensal sensitization and 33 antigens were found to discriminate convalescent candidemia from non-candidemia controls. The sensitivity and specificity for the identification of acute candidemia determined by the top 10 antigens from the set of 13 serodiagnostic markers are comparable to that obtained using the method of 2D-PAGE and immunoblots [17] . When using the top 5 antigens from the set of 33, both sensitivity and specificity are dramatically improved for convalescent candidemia. Pitarch et al. reported that the anti-Bgl2p IgG antibody levels mainly define the proteomic signature for candidemia patients [17] . In this study, Bgl2 is on the list of 33 diagnostic antigens from convalescent sera. Although it is classified as a serodominant antigen by acute candidemia sera, the BHadjusted p-value of Bgl2 (0.116) is just above cutoff (0.05) to be considered as diagnostic by our definition, and the mean anti-Bgl2 antibodies in acute candidemia is higher than the mean in noncandidemia controls. Bgl2 is a glycoprotein and the glycan moieties on other b-1,3-glucanosyltransferases seem to contribute to antigenicity. Since our Bgl2 is expressed in vitro without any glycosylation, its antigenicity is likely different from the Bgl2 produced by C. albicans used in the 2D-PAGE immunoblots. The previously identified immunogenic heat shock protein 90 (Hsp90) is also one of 33 biomarkers for convalescent candidemia identified from this study. Hsp90 has been shown to elicit a protective humoral response [42, 43] and its antibodies are known to associate with patients that recover from candidiasis. The use of protein microarray technology allowed us to identify new diagnostic antigens that were missed by previous studies. The use of 2-D PAGE to accurately identify and separate clinical markers of candidemia from commensal sensitization is limited by the range in protein abundance and various properties associated with peptides such as their mass, isoelectric point, hydrophobicity, and post-translational modification, as well as the semi-quantitative nature of a Western [18] . Using a C. albicans cell surface protein microarray helped us overcome many of the technical difficulties found with traditional proteomics, since the expression level of recombinant-derived proteins vary by only a single log and the use of fluorescent-labeled antibodies allows for greater linearity, precision, and sensitivity in the quantitative measurement of the humoral response to C. albicans. One of the most beneficial aspects in the use of the protein microarray assay is its ability to detect significant differences in the IgG response that under traditional immunoblot conditions would be below the detectable threshold. However, a potential limitation to our study is that the microarray is based on recombinant peptides. Because of the cell free nature of our in vitro translated peptides, potential epitopes may have been lost due to miss folding and a lack of glycosylation, both of which may affect the conformational structure of the native protein. On the other hand, the removal of posttranslational modifications, such as glycosylation, from the peptides may have revealed hidden peptide epitopes only seen during a strong host immune response. A large collection of peptide epitopes may increase the specificity in diagnosis of infection. In support of this, our study has identified many new clinical biomarkers that are associated with differing states of interactions with the host as well as the characterization of potential new targets for therapeutics and vaccine candidates. To our knowledge, this is the first study using a protein microarray to analyze the serological response to an organism that is capable of existing as both commensal flora and an opportunistic pathogen in the human population.