Combination of Cytokine Responses Indicative of Latent TB and Active TB in Malawian Adults.


Hur, YG; Gorak-Stolinska, P; Ben-Smith, A; Lalor, MK; Chaguluka, S; Dacombe, R; Doherty, TM; Ottenhoff, TH; Dockrell, HM; Crampin, AC; (2013) Combination of Cytokine Responses Indicative of Latent TB and Active TB in Malawian Adults. PLoS One, 8 (11). e79742. ISSN 1932-6203 DOI: 10.1371/journal.pone.0079742

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Abstract

BACKGROUND An IFN-γ response to M. tuberculosis-specific antigens is an effective biomarker for M. tuberculosis infection but it cannot discriminate between latent TB infection and active TB disease. Combining a number of cytokine/chemokine responses to M. tuberculosis antigens may enable differentiation of latent TB from active disease. METHODS Asymptomatic recently-exposed individuals (spouses of TB patients) were recruited and tuberculin skin tested, bled and followed-up for two years. Culture supernatants, from a six-day culture of diluted whole blood samples stimulated with M. tuberculosis-derived PPD or ESAT-6, were measured for IFN-γ, IL-10, IL-13, IL-17, TNF-α and CXCL10 using cytokine ELISAs. In addition, 15 patients with sputum smear-positive pulmonary TB were recruited and tested. RESULTS Spouses with positive IFN-γ responses to M. tuberculosis ESAT-6 (>62.5 pg/mL) and TB patients showed high production of IL-17, CXCL10 and TNF-α. Higher production of IL-10 and IL-17 in response to ESAT-6 was observed in the spouses compared with TB patients while the ratios of IFN-γ/IL-10 and IFN-γ/IL-17 in response to M. tuberculosis-derived PPD were significantly higher in TB patients compared with the spouses. Tuberculin skin test results did not correlate with cytokine responses. CONCLUSIONS CXCL10 and TNF-α may be used as adjunct markers alongside an IFN-γ release assay to diagnose M. tuberculosis infection, and IL-17 and IL-10 production may differentiate individuals with LTBI from active TB.

Item Type: Article
Faculty and Department: Academic Services & Administration > Academic Administration
Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Faculty of Infectious and Tropical Diseases > Dept of Clinical Research
Research Centre: TB Centre
MEIRU
The International Centre for Evidence in Disability
Centre for Global Non-Communicable Diseases (NCDs)
PubMed ID: 24260295
Web of Science ID: 327308500096
URI: http://researchonline.lshtm.ac.uk/id/eprint/1367687

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