Mycobacteria-specific cytokine responses as correlates of treatment response in active and latent tuberculosis

Clifford, Vanessa, Tebruegge, Marc, Zufferey, Christel, Germano, Susie, Forbes, Ben, Cosentino, Lucy, McBryde, Emma, Eisen, Damon, Robins-Browne, Roy, Street, Alan, Denholm, Justin, and Curtis, Nigel (2017) Mycobacteria-specific cytokine responses as correlates of treatment response in active and latent tuberculosis. Journal of Infection, 75. 132 - 145.

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Abstract

Objectives: A biomarker indicating successful tuberculosis (TB) therapy would assist in determining appropriate length of treatment. This study aimed to determine changes in mycobacteria-specific antigen-induced cytokine biomarkers in patients receiving therapy for latent or active TB, to identify biomarkers potentially correlating with treatment success.

Methods: A total of 33 adults with active TB and 36 with latent TB were followed longitudinally over therapy. Whole blood stimulation assays using mycobacteria-specific antigens (CFP-10, ESAT-6, PPD) were done on samples obtained at 0, 1, 3, 6 and 9 months. Cytokine responses (IFN-γ, IL-1ra, IL-2, IL-10, IL-13, IP-10, MIP-1β, and TNF-α) in supernatants were measured by Luminex xMAP immunoassay.

Results: In active TB cases, median IL-1ra (with CFP-10 and with PPD stimulation), IP-10 (CFP-10, ESAT-6), MIP-1β (ESAT-6, PPD), and TNF-α (ESAT-6) responses declined significantly over the course of therapy. In latent TB cases, median IL-1ra (CFP-10, ESAT-6, PPD), IL-2 (CFP-10, ESAT-6), and IP-10 (CFP-10, ESAT-6) responses declined significantly.

Conclusions: Mycobacteria-specific cytokine responses change significantly over the course of therapy, and their kinetics in active TB differ from those observed in latent TB. In particular, mycobacteria-specific IL-1ra responses are potential correlates of successful therapy in both active and latent TB.

Item ID: 51409
Item Type: Article (Research - C1)
ISSN: 1532-2742
Keywords: tuberculosis, cytokines, biomarkers, latent TB, active TB, monitoring
Funders: John Burge Trust Fund, Australian Government Research Training Scholarship
Date Deposited: 07 Nov 2017 03:30
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110309 Infectious Diseases @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110303 Clinical Microbiology @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920115 Respiratory System and Diseases (incl. Asthma) @ 50%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 50%
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