PLoS ONE (Jan 2012)

Potential of host markers produced by infection phase-dependent antigen-stimulated cells for the diagnosis of tuberculosis in a highly endemic area.

  • Novel N Chegou,
  • Paulin N Essone,
  • Andre G Loxton,
  • Kim Stanley,
  • Gillian F Black,
  • Gian D van der Spuy,
  • Paul D van Helden,
  • Kees L Franken,
  • Shreemanta K Parida,
  • Michel R Klein,
  • Stefan H E Kaufmann,
  • Tom H M Ottenhoff,
  • Gerhard Walzl

DOI
https://doi.org/10.1371/journal.pone.0038501
Journal volume & issue
Vol. 7, no. 6
p. e38501

Abstract

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BACKGROUND: Recent interferon gamma (IFN-γ)-based studies have identified novel Mycobacterium tuberculosis (M.tb) infection phase-dependent antigens as diagnostic candidates. In this study, the levels of 11 host markers other than IFN-γ, were evaluated in whole blood culture supernatants after stimulation with M.tb infection phase-dependent antigens, for the diagnosis of TB disease. METHODOLOGY AND PRINCIPAL FINDINGS: Five M.tb infection phase-dependent antigens, comprising of three DosR-regulon-encoded proteins (Rv2032, Rv0081, Rv1737c), and two resucitation promoting factors (Rv0867c and Rv2389c), were evaluated in a case-control study with 15 pulmonary TB patients and 15 household contacts that were recruited from a high TB incidence setting in Cape Town, South Africa. After a 7-day whole blood culture, supernatants were harvested and the levels of the host markers evaluated using the Luminex platform. Multiple antigen-specific host markers were identified with promising diagnostic potential. Rv0081-specific levels of IL-12(p40), IP-10, IL-10 and TNF-α were the most promising diagnostic candidates, each ascertaining TB disease with an accuracy of 100%, 95% confidence interval for the area under the receiver operating characteristics plots, (1.0 to 1.0). CONCLUSIONS: Multiple cytokines other than IFN-γ in whole blood culture supernatants after stimulation with M.tb infection phase-dependent antigens show promise as diagnostic markers for active TB. These preliminary findings should be verified in well-designed diagnostic studies employing short-term culture assays.