TY - JOUR
T1 - Cytokine biomarkers for the diagnosis of tuberculosis infection and disease in adults in a low prevalence setting
AU - Clifford, Vanessa
AU - Tebruegge, Marc
AU - Zufferey, Christel
AU - Germano, Susie
AU - Forbes, Ben
AU - Cosentino, Lucy
AU - Matchett, Elizabeth
AU - McBryde, Emma
AU - Eisen, Damon
AU - Robins-Browne, Roy
AU - Street, Alan
AU - Denholm, Justin
AU - Curtis, Nigel
PY - 2019/1
Y1 - 2019/1
N2 - Objective: Accurate and timely diagnosis of tuberculosis (TB) is essential to control the global pandemic. Currently available immunodiagnostic tests cannot discriminate between latent tuberculosis infection (LTBI) and active tuberculosis. This study aimed to determine whether candidate mycobacterial antigen-stimulated cytokine biomarkers can discriminate between TB-uninfected and TB-infected adults, and additionally between LTBI and active TB disease. Methods: 193 adults were recruited, and categorised into four unambiguous diagnostic groups: microbiologically-proven active TB, LTBI, sick controls (non-TB lower respiratory tract infections) and healthy controls. Whole blood assays were used to determine mycobacterial antigen (CFP-10, ESAT-6, PPD)-stimulated cytokine (IL-1ra, IL-2, IL-10, IL-13, TNF-α IFN-γ IP-10 and MIP-1β) responses, measured by Luminex multiplex immunoassay. Results: The background-corrected mycobacterial antigen-stimulated cytokine responses of all eight cytokines were significantly higher in TB-infected participants compared with TB-uninfected individuals, with IL-2 showing the best performance characteristics. In addition, mycobacterial antigen-stimulated responses with IL-1ra, IL-10 and TNF-α were higher in participants with active TB compared those with LTBI, reaching statistical significance with PPD stimulation, although there was a degree of overlap between the two groups. Conclusion: Mycobacterial antigen-stimulated cytokine responses may prove useful in future immunodiagnostic tests to discriminate between tuberculosis-infected and tuberculosis-uninfected individual, and potentially between LTBI and active tuberculosis.
AB - Objective: Accurate and timely diagnosis of tuberculosis (TB) is essential to control the global pandemic. Currently available immunodiagnostic tests cannot discriminate between latent tuberculosis infection (LTBI) and active tuberculosis. This study aimed to determine whether candidate mycobacterial antigen-stimulated cytokine biomarkers can discriminate between TB-uninfected and TB-infected adults, and additionally between LTBI and active TB disease. Methods: 193 adults were recruited, and categorised into four unambiguous diagnostic groups: microbiologically-proven active TB, LTBI, sick controls (non-TB lower respiratory tract infections) and healthy controls. Whole blood assays were used to determine mycobacterial antigen (CFP-10, ESAT-6, PPD)-stimulated cytokine (IL-1ra, IL-2, IL-10, IL-13, TNF-α IFN-γ IP-10 and MIP-1β) responses, measured by Luminex multiplex immunoassay. Results: The background-corrected mycobacterial antigen-stimulated cytokine responses of all eight cytokines were significantly higher in TB-infected participants compared with TB-uninfected individuals, with IL-2 showing the best performance characteristics. In addition, mycobacterial antigen-stimulated responses with IL-1ra, IL-10 and TNF-α were higher in participants with active TB compared those with LTBI, reaching statistical significance with PPD stimulation, although there was a degree of overlap between the two groups. Conclusion: Mycobacterial antigen-stimulated cytokine responses may prove useful in future immunodiagnostic tests to discriminate between tuberculosis-infected and tuberculosis-uninfected individual, and potentially between LTBI and active tuberculosis.
KW - Active TB
KW - Biomarkers
KW - Cytokines
KW - Diagnostics
KW - LTBI
KW - Tuberculosis
UR - http://www.scopus.com/inward/record.url?scp=85058556592&partnerID=8YFLogxK
U2 - 10.1016/j.tube.2018.08.011
DO - 10.1016/j.tube.2018.08.011
M3 - Article
C2 - 30711163
AN - SCOPUS:85058556592
SN - 1472-9792
VL - 114
SP - 91
EP - 102
JO - Tuberculosis
JF - Tuberculosis
ER -