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

Yanyan Liu,Thumbi Ndung’U,Douglas Wilson,Ryung Kim,Okechukwu Ndumnego,Jacqueline Achkar,Elizabeth Jenny-Avital,Tingting Chen

doi:10.3390/pathogens7010026

Abstract

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.

Highlights

IntroductionIn 2016, an estimated 1.3 million and 0.4 million deaths were reported due to TB among HIV uninfected and co-infected persons, respectively [1]
Active tuberculosis (TB) is the leading cause of death from a single infectious agent worldwide [1].In 2016, an estimated 1.3 million and 0.4 million deaths were reported due to TB among HIV uninfected and co-infected persons, respectively [1]
Our receiver operating characteristic (ROC) curve analysis was based on HIV-infected smear-negative culture-confirmed TB patients and South African HIV-infected controls enrolled in the same setting (Figure 2)

Summary

Introduction

In 2016, an estimated 1.3 million and 0.4 million deaths were reported due to TB among HIV uninfected and co-infected persons, respectively [1]. Pathogens 2018, 7, 26 risk of developing TB within the first five years post-infection [2,3]. Co-infection with HIV increases the lifetime risk of developing active TB to about 30–60%, rising as host immunity deteriorates [4,5]. Sputum microscopy for acid-fast bacilli (AFB), the most commonly used rapid point-of-care (POC) test for TB, typically has a sensitivity below 50%, with numbers reported to be as low as 10% for HIV-associated TB in some screening studies [10,11]

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Conclusion