Immune Profiling With a Salmonella Typhi Antigen Microarray Identifies New Diagnostic Biomarkers of Human Typhoid

Sci Rep. 2013;3:1043. doi: 10.1038/srep01043. Epub 2013 Jan 9.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Bacterial / analysis*
  • Antigens / genetics
  • Antigens / immunology*
  • Antigens / metabolism
  • Biomarkers / analysis
  • Cloning, Molecular
  • Humans
  • Immunoglobulin G / analysis
  • Immunoglobulin M / analysis
  • Protein Array Analysis*
  • Proteome / immunology
  • Proteome / metabolism
  • ROC Curve
  • Salmonella typhi / metabolism*
  • Sensitivity and Specificity
  • Typhoid Fever / diagnosis*

Substances

  • Antibodies, Bacterial
  • Antigens
  • Biomarkers
  • Immunoglobulin G
  • Immunoglobulin M
  • Proteome