Host Protein Biomarkers Identify Active Tuberculosis in HIV Uninfected and Co-infected Individuals

Jacqueline M. Achkar, Laetitia Cortes, Pascal Croteau, Corey Yanofsky, Marija Mentinova, Isabelle Rajotte, Michael Schirm, Yiyong Zhou, Ana Paula Junqueira-Kipnis, Victoria O. Kasprowicz, Michelle H. Larsen, René Allard, Joanna Hunter, Eustache Paramithiotis

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Biomarkers for active tuberculosis (TB) are urgently needed to improve rapid TB diagnosis. The objective of this study was to identify serum protein expression changes associated with TB but not latent Mycobacterium tuberculosis infection (LTBI), uninfected states, or respiratory diseases other than TB (ORD). Serum samples from 209 HIV uninfected (HIV-) and co-infected (HIV+) individuals were studied. In the discovery phase samples were analyzed via liquid chromatography and mass spectrometry, and in the verification phase biologically independent samples were analyzed via a multiplex multiple reaction monitoring mass spectrometry (MRM-MS) assay. Compared to LTBI and ORD, host proteins were significantly differentially expressed in TB, and involved in the immune response, tissue repair, and lipid metabolism. Biomarker panels whose composition differed according to HIV status, and consisted of 8 host proteins in HIV- individuals (CD14, SEPP1, SELL, TNXB, LUM, PEPD, QSOX1, COMP, APOC1), or 10 host proteins in HIV+ individuals (CD14, SEPP1, PGLYRP2, PFN1, VASN, CPN2, TAGLN2, IGFBP6), respectively, distinguished TB from ORD with excellent accuracy (AUC=0.96 for HIV- TB, 0.95 for HIV+ TB). These results warrant validation in larger studies but provide promise that host protein biomarkers could be the basis for a rapid, blood-based test for TB.

Original languageEnglish (US)
Pages (from-to)1160-1168
Number of pages9
JournalEBioMedicine
Volume2
Issue number9
DOIs
Publication statusPublished - Sep 1 2015

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Keywords

  • Biomarker
  • Diagnostics
  • Host proteins
  • Tuberculosis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Achkar, J. M., Cortes, L., Croteau, P., Yanofsky, C., Mentinova, M., Rajotte, I., ... Paramithiotis, E. (2015). Host Protein Biomarkers Identify Active Tuberculosis in HIV Uninfected and Co-infected Individuals. EBioMedicine, 2(9), 1160-1168. https://doi.org/10.1016/j.ebiom.2015.07.039