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Article

Soluble CD14 as a Diagnostic Biomarker for Smear-Negative HIV-Associated Tuberculosis

1
Department of Medicine, Albert Einstein College of Medicine, New York, NY 10461, USA
2
Africa Health Research Institute, Durban 4013, South Africa
3
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, NY 10461, USA
4
HIV Pathogenesis Programme, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban 4013, South Africa
5
Ragon Institute of MGH, MIT and Harvard University, Cambridge, MA 02139, USA
6
Max Planck Institute of Infection Biology, 10117 Berlin, Germany
7
Department of Medicine, Edendale Hospital, University of KwaZulu-Natal, Pietermaritzburg 3201, South Africa
8
Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY 10461, USA
*
Author to whom correspondence should be addressed.
Both authors contributed equally to this work.
Pathogens 2018, 7(1), 26; https://doi.org/10.3390/pathogens7010026
Received: 25 January 2018 / Revised: 20 February 2018 / Accepted: 21 February 2018 / Published: 27 February 2018
(This article belongs to the Special Issue Mechanisms of Mycobacterium tuberculosis Pathogenesis)
Sputum smear-negative HIV-associated active tuberculosis (TB) is challenging to diagnose. CD14 is a pattern recognition receptor that is known to mediate monocyte activation. Prior studies have shown increased levels of soluble CD14 (sCD14) as a potential biomarker for TB, but little is known about its value in detecting smear-negative HIV-associated TB. We optimized a sandwich ELISA for the detection of sCD14, and tested sera from 56 smear-negative South African (39 culture-positive and 17 culture-negative) HIV-infected pulmonary TB patients and 24 South African and 43 US (21 positive and 22 negative for tuberculin skin test, respectively) HIV-infected controls. SCD14 concentrations were significantly elevated in smear-negative HIV-associated TB compared with the HIV-infected controls (p < 0.0001), who had similar concentrations, irrespective of the country of origin or the presence or absence of latent M. tuberculosis infection (p = 0.19). The culture-confirmed TB group had a median sCD14 level of 2199 ng/mL (interquartile range 1927–2719 ng/mL), versus 1148 ng/mL (interquartile range 1053–1412 ng/mL) for the South African controls. At a specificity of 96%, sCD14 had a sensitivity of 95% for culture-confirmed smear-negative TB. These data indicate that sCD14 could be a highly accurate biomarker for the detection of HIV-associated TB. View Full-Text
Keywords: tuberculosis; biomarker; diagnostics; HIV; CD14; C-reactive protein tuberculosis; biomarker; diagnostics; HIV; CD14; C-reactive protein
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MDPI and ACS Style

Liu, Y.; Ndumnego, O.C.; Chen, T.; Kim, R.S.; Jenny-Avital, E.R.; Ndung’u, T.; Wilson, D.; Achkar, J.M. Soluble CD14 as a Diagnostic Biomarker for Smear-Negative HIV-Associated Tuberculosis. Pathogens 2018, 7, 26. https://doi.org/10.3390/pathogens7010026

AMA Style

Liu Y, Ndumnego OC, Chen T, Kim RS, Jenny-Avital ER, Ndung’u T, Wilson D, Achkar JM. Soluble CD14 as a Diagnostic Biomarker for Smear-Negative HIV-Associated Tuberculosis. Pathogens. 2018; 7(1):26. https://doi.org/10.3390/pathogens7010026

Chicago/Turabian Style

Liu, Yanyan, Okechukwu C. Ndumnego, Tingting Chen, Ryung S. Kim, Elizabeth R. Jenny-Avital, Thumbi Ndung’u, Douglas Wilson, and Jacqueline M. Achkar 2018. "Soluble CD14 as a Diagnostic Biomarker for Smear-Negative HIV-Associated Tuberculosis" Pathogens 7, no. 1: 26. https://doi.org/10.3390/pathogens7010026

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