TY - JOUR
T1 - Soluble CD14 as a diagnostic biomarker for smear-negative HIV-associated tuberculosis
AU - Liu, Yanyan
AU - Ndumnego, Okechukwu C.
AU - Chen, Tingting
AU - Kim, Ryung S.
AU - Jenny-Avital, Elizabeth R.
AU - Ndung’u, Thumbi
AU - Wilson, Douglas
AU - Achkar, Jacqueline M.
N1 - Funding Information:
The work was supported in part by funds from the National Institute of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID; AI117927, AI105684, and AI067665 to JMA) and the Einstein-Rockefeller-CUNY Center for AIDS Research (P30-AI124414). This work was further supported through the Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE), a DELTAS Africa Initiative (DEL-15-006). The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS)’s Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa’s Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust (107752/Z/15/Z) and the UK government. The views expressed in this publication are those of the author(s) and not necessarily those of AAS, NEPAD Agency, Welcome Trust or the UK government.
Funding Information:
Acknowledgments: The work was supported in part by funds from the National Institute of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID; AI117927, AI105684, and AI067665 to JMA) and the Einstein-Rockefeller-CUNY Center for AIDS Research (P30-AI124414). This work was further supported through the Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE), a DELTAS Africa Initiative (DEL-15-006). The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS)’s Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa’s Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust (107752/Z/15/Z) and the UK government. The views expressed in this publication are those of the author(s) and not necessarily those of AAS, NEPAD Agency, Welcome Trust or the UK government.
Publisher Copyright:
© 2018 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2018/3
Y1 - 2018/3
N2 - 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.
AB - 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.
KW - Biomarker
KW - C-reactive protein
KW - CD14
KW - Diagnostics
KW - HIV
KW - Tuberculosis
UR - http://www.scopus.com/inward/record.url?scp=85048291975&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85048291975&partnerID=8YFLogxK
U2 - 10.3390/pathogens7010026
DO - 10.3390/pathogens7010026
M3 - Article
AN - SCOPUS:85048291975
SN - 2076-0817
VL - 7
JO - Pathogens
JF - Pathogens
IS - 1
M1 - 26
ER -
