Host Protein Biomarkers Identify Active Tuberculosis in HIV Uninfected and Co-infected Individuals.
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.
Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA ; Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA.
Jacqueline M
JM
Achkar
Caprion Proteomics Inc., 201 President-Kennedy Ave., Montreal H2X 3Y7, Quebec, Canada.
Laetitia
L
Cortes
Caprion Proteomics Inc., 201 President-Kennedy Ave., Montreal H2X 3Y7, Quebec, Canada.
Pascal
P
Croteau
Caprion Proteomics Inc., 201 President-Kennedy Ave., Montreal H2X 3Y7, Quebec, Canada.
Corey
C
Yanofsky
Caprion Proteomics Inc., 201 President-Kennedy Ave., Montreal H2X 3Y7, Quebec, Canada.
Marija
M
Mentinova
Caprion Proteomics Inc., 201 President-Kennedy Ave., Montreal H2X 3Y7, Quebec, Canada.
Isabelle
I
Rajotte
Caprion Proteomics Inc., 201 President-Kennedy Ave., Montreal H2X 3Y7, Quebec, Canada.
Michael
M
Schirm
Caprion Proteomics Inc., 201 President-Kennedy Ave., Montreal H2X 3Y7, Quebec, Canada.
Yiyong
Y
Zhou
Department of Microbiology, Immunology, Parasitology and Pathology, Public Health and Tropical Medicine Institute, Federal University of Goias, Rua 235 esq. Primeira avenida, Goiania, Goias, 74605-050, Brazil.
Ana Paula
AP
Junqueira-Kipnis
KwaZulu-Natal Research Institute for TB HIV (K-RITH), KwaZulu-Natal, Durban, South Africa ; The Ragon Institute of MGH, MIT and Harvard, Charlestown, Boston, USA ; HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
Victoria O
VO
Kasprowicz
Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA.
Michelle
M
Larsen
Caprion Proteomics Inc., 201 President-Kennedy Ave., Montreal H2X 3Y7, Quebec, Canada.
René
R
Allard
Caprion Proteomics Inc., 201 President-Kennedy Ave., Montreal H2X 3Y7, Quebec, Canada.
Joanna
J
Hunter
Caprion Proteomics Inc., 201 President-Kennedy Ave., Montreal H2X 3Y7, Quebec, Canada.
Eustache
E
Paramithiotis
D000328:Adult; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood*; D001798:Blood Proteins / Q000378:metabolism; D060085:Coinfection / Q000150:complications*; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D008297:Male; D008875:Middle Aged; D014376:Tuberculosis / Q000097:blood / Q000150:complications*
D015415:Biomarkers; D001798:Blood Proteins
Biomarker; Diagnostics; Host proteins; Tuberculosis