title: Plasma heme oxygenase-1 levels distinguish latent or successfully treated human tuberculosis from active disease.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratory of Parasitic Diseases, National Institutes of Health, Bethesda, Maryland, United States of America. bruno.andrade@nih.gov
authors.forename: Bruno B
authors.initials: BB
authors.lastname: Andrade
authors.forename: Nathella
authors.initials: N
authors.lastname: Pavan Kumar
authors.forename: Katrin D
authors.initials: KD
authors.lastname: Mayer-Barber
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Barber
authors.forename: Rathinam
authors.initials: R
authors.lastname: Sridhar
authors.forename: Vaithilingam V Banu
authors.initials: VV
authors.lastname: Rekha
authors.forename: Mohideen S
authors.initials: MS
authors.lastname: Jawahar
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Nutman
authors.forename: Alan
authors.initials: A
authors.lastname: Sher
authors.forename: Subash
authors.initials: S
authors.lastname: Babu
mesh_terms: D000210:Acute-Phase Reaction; D000293:Adolescent; D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood; D003937:Diagnosis, Differential; D005260:Female; D051547:Heme Oxygenase-1 / Q000097:blood*; D006801:Humans; D055985:Latent Tuberculosis / Q000097:blood* / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis; D011446:Prospective Studies; D012372:ROC Curve; D013183:Sputum / Q000382:microbiology; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D015415:Biomarkers; D016207:Cytokines; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1