title: 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.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of California, Irvine, CA 92697, USA. lliang3@uci.edu
authors.forename: Li
authors.initials: L
authors.lastname: Liang
authors.forename: Silvia
authors.initials: S
authors.lastname: Juarez
authors.forename: Tran Vu Thieu
authors.initials: TV
authors.lastname: Nga
authors.forename: Sarah
authors.initials: S
authors.lastname: Dunstan
authors.forename: Rie
authors.initials: R
authors.lastname: Nakajima-Sasaki
authors.forename: D Huw
authors.initials: DH
authors.lastname: Davies
authors.forename: Stephen
authors.initials: S
authors.lastname: McSorley
authors.forename: Stephen
authors.initials: S
authors.lastname: Baker
authors.forename: Philip L
authors.initials: PL
authors.lastname: Felgner
mesh_terms: D000907:Antibodies, Bacterial / Q000032:analysis*; D000941:Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis; D003001:Cloning, Molecular; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D040081:Protein Array Analysis; D020543:Proteome / Q000276:immunology / Q000378:metabolism; D012372:ROC Curve; D012485:Salmonella typhi / Q000378:metabolism*; D012680:Sensitivity and Specificity; D014435:Typhoid Fever / Q000175:diagnosis*
chemical_list: D000907:Antibodies, Bacterial; D000941:Antigens; D015415:Biomarkers; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D020543:Proteome