Combination of cytokine responses indicative of latent TB and active TB in Malawian adults

Kumar, A. et al. (2013) Combination of cytokine responses indicative of latent TB and active TB in Malawian adults. PLoS ONE, 8(11), e79742. (doi: 10.1371/journal.pone.0079742) (PMID:24260295) (PMCID:PMC3832606)

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: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Crampin, Professor Mia
• Authors: Kumar, A., Hur, Y.-G., Gorak-Stolinska, P., Ben-Smith, A., Lalor, M. K., Chaguluka, S., Dacombe, R., Doherty, T. M., Ottenhoff, T. H., Dockrell, H. M., and Crampin, A. C.
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Public Health
• Journal Name: PLoS ONE
• Publisher: Public Library of Science
• ISSN: 1932-6203
• ISSN (Online): 1932-6203
• Copyright Holders: Copyright © 2013 Hur et al.
• First Published: First published in PLoS ONE 8(11):e79742
• Publisher Policy: Reproduced under a Creative Commons License