Plasma Heme oxygenase-1 Levels Distinguish Latent or Successfully Treated Human Tuberculosis From Active Disease

PLoS One. 2013 May 6;8(5):e62618. doi: 10.1371/journal.pone.0062618. Print 2013.

Abstract

Background: Tuberculosis (TB) is associated with oxidative stress and the induction of host anti-oxidants to counteract this response. Heme oxygenase-1 (HO-1) is a critical promoter of cytoprotection in diverse disease models including mycobacterial infection. Nevertheless, the pattern of expression of HO-1 in human tuberculosis has not been studied. Here, we examine expression of HO-1 in M. tuberculosis-exposed and -infected individuals and test its ability to distinguish active from latent and successfully treated TB cases. In addition, we assess correlations between plasma levels of HO-1 and cytokines closely associated with the immunopathogenesis of TB.

Methods: Cross-sectional and longitudinal analyses of levels of HO-1, acute phase proteins and pro-inflammatory cytokines were performed in plasma samples from individuals with active pulmonary, extra-pulmonary or latent TB infection and healthy controls as part of a prospective cohort study in South India.

Results: Systemic levels of HO-1 were dramatically increased in individuals with active pulmonary and extra-pulmonary tuberculosis and particularly those with bilateral lung lesions and elevated bacillary loads in sputum. HO-1 levels effectively discriminated active from latent tuberculosis with higher predictive values than either C-reactive protein or serum amyloid protein. Moreover, there was a marked reduction in HO-1 levels in active TB cases following anti-tuberculous therapy but not in those who failed treatment. Pulmonary TB patients displaying the highest concentrations of HO-1 in plasma exhibited significantly elevated plasma levels of interleukin (IL)-10, interferon (IFN)-γ and IL-17 and diminished levels of tumor necrosis factor (TNF)-α.

Conclusion: These findings establish HO-1 levels as a potentially useful parameter for distinguishing active from latent or treated pulmonary tuberculosis, that is superior in this respect to the measurement of other acute inflammatory proteins.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Acute-Phase Reaction
  • Adolescent
  • Adult
  • Aged
  • Antitubercular Agents / therapeutic use
  • Biomarkers / blood
  • Case-Control Studies
  • Cytokines / blood
  • Diagnosis, Differential
  • Female
  • Heme Oxygenase-1 / blood*
  • Humans
  • Latent Tuberculosis / blood*
  • Latent Tuberculosis / diagnosis
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis*
  • Prospective Studies
  • ROC Curve
  • Sputum / microbiology
  • Treatment Outcome
  • Tuberculosis, Pulmonary / blood*
  • Tuberculosis, Pulmonary / diagnosis
  • Tuberculosis, Pulmonary / drug therapy
  • Young Adult

Substances

  • Antitubercular Agents
  • Biomarkers
  • Cytokines
  • HMOX1 protein, human
  • Heme Oxygenase-1