Immune profiling with a Salmonella Typhi antigen microarray identifies new diagnostic biomarkers of human typhoid

Abstract

Current serological diagnostic assays for typhoid fever are based on detecting antibodies against Salmonella LPS or flagellum, resulting in a high false-positive rate. Here we used a protein microarray containing 2,724 Salmonella enterica serovar Typhi antigens (>63% of proteome) and identified antibodies against 16 IgG antigens and 77 IgM antigens that were differentially reactive among acute typhoid patients and healthy controls. The IgG target antigens produced a sensitivity of 97% and specificity of 80%, whereas the IgM target antigens produced 97% and 91% sensitivity and specificity, respectively. Our analyses indicated certain features such as membrane association, secretion, and protein expression were significant enriching features of the reactive antigens. About 72% of the serodiagnostic antigens were within the top 25% of the ranked antigen list using a Naïve bayes classifier. These data provide an important resource for improved diagnostics, therapeutics and vaccine development against an important human pathogen.