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Pathogens 2018, 7(1), 26;

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

Department of Medicine, Albert Einstein College of Medicine, New York, NY 10461, USA
Africa Health Research Institute, Durban 4013, South Africa
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, NY 10461, USA
HIV Pathogenesis Programme, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban 4013, South Africa
Ragon Institute of MGH, MIT and Harvard University, Cambridge, MA 02139, USA
Max Planck Institute of Infection Biology, 10117 Berlin, Germany
Department of Medicine, Edendale Hospital, University of KwaZulu-Natal, Pietermaritzburg 3201, South Africa
Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY 10461, USA
Both authors contributed equally to this work.
Author to whom correspondence should be addressed.
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)
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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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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.

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