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

被引:47
作者
Achkar, Jacqueline M. [1 ,2 ]
Cortes, Laetitia [3 ]
Croteau, Pascal [3 ]
Yanofsky, Corey [3 ]
Mentinova, Marija [3 ]
Rajotte, Isabelle [3 ]
Schirm, Michael [3 ]
Zhou, Yiyong [3 ]
Junqueira-Kipnis, Ana Paula [4 ]
Kasprowicz, Victoria O. [5 ,6 ,7 ]
Larsen, Michelle [1 ]
Allard, Rene [3 ]
Hunter, Joanna [3 ]
Paramithiotis, Eustache [3 ]
机构
[1] Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA
[2] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA
[3] Caprion Prote Inc, Montreal, PQ H2X 3Y7, Canada
[4] Univ Fed Goias, Publ Hlth & Trop Med Inst, Dept Microbiol Immunol Parasitol & Pathol, BR-74605050 Goiania, Go, Brazil
[5] KwaZulu Natal Res Inst TB HIV K RITH, Durban, South Africa
[6] Ragon Inst MGH MIT & Harvard, Boston, MA USA
[7] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Doris Duke Med Res Inst, HIV Pathogenesis Programme, Durban, South Africa
关键词
Tuberculosis; Biomarker; Diagnostics; Host proteins; MYCOBACTERIUM-TUBERCULOSIS; PULMONARY TUBERCULOSIS; LIPOPROTEIN METABOLISM; PROTEOMIC ANALYSIS; RNA EXPRESSION; SOLUBLE CD14; SERUM; DIAGNOSIS; BINDING; INFLAMMATION;
D O I
10.1016/j.ebiom.2015.07.039
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. (C) 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
引用
收藏
页码:1160 / 1168
页数:9
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