TY - JOUR
T1 - Host Protein Biomarkers Identify Active Tuberculosis in HIV Uninfected and Co-infected Individuals
AU - Achkar, Jacqueline M.
AU - Cortes, Laetitia
AU - Croteau, Pascal
AU - Yanofsky, Corey
AU - Mentinova, Marija
AU - Rajotte, Isabelle
AU - Schirm, Michael
AU - Zhou, Yiyong
AU - Junqueira-Kipnis, Ana Paula
AU - Kasprowicz, Victoria O.
AU - Larsen, Michelle
AU - Allard, René
AU - Hunter, Joanna
AU - Paramithiotis, Eustache
N1 - Funding Information:
This work was funded by the National Institute of Health (NIH)/ National Institute of Allergy and Infectious Diseases (NIAID) contract HHSN272200800047C to E. P., and in part by AI067665, AI096213 and AI105684 to J. M. A., and the Center for AIDS Research (CFAR) at the Albert Einstein College of Medicine (AI-51519; J. M. A.).
Funding Information:
This work was funded by the National Institute of Health (NIH)/ National Institute of Allergy and Infectious Diseases (NIAID) contract HHSN272200800047C to E.P., and in part by AI067665 , AI096213 and AI105684 to J.M.A., and the Center for AIDS Research (CFAR) at the Albert Einstein College of Medicine ( AI-51519 ; J.M.A.).
Publisher Copyright:
© 2015.
PY - 2015/9/1
Y1 - 2015/9/1
N2 - 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.
AB - 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.
KW - Biomarker
KW - Diagnostics
KW - Host proteins
KW - Tuberculosis
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U2 - 10.1016/j.ebiom.2015.07.039
DO - 10.1016/j.ebiom.2015.07.039
M3 - Article
C2 - 26501113
AN - SCOPUS:84953733731
SN - 2352-3964
VL - 2
SP - 1160
EP - 1168
JO - EBioMedicine
JF - EBioMedicine
IS - 9
ER -
