title: Host markers in QuantiFERON supernatants differentiate active TB from latent TB infection: preliminary report.
abstract: BACKGROUND
  Interferon gamma release assays, including the QuantiFERON TB Gold In Tube (QFT) have been shown to be accurate in diagnosing Mycobacterium tuberculosis infection. These assays however, do not discriminate between latent TB infection (LTBI) and active TB disease.
  
  
  METHODS
  We recruited twenty-three pulmonary TB patients and 34 household contacts from Cape Town, South Africa and performed the QFT test. To investigate the ability of new host markers to differentiate between LTBI and active TB, levels of 29 biomarkers in QFT supernatants were evaluated using a Luminex multiplex cytokine assay.
  
  
  RESULTS
  Eight out of 29 biomarkers distinguished active TB from LTBI in a pilot study. Baseline levels of epidermal growth factor (EGF) soluble CD40 ligand (sCD40L), antigen stimulated levels of EGF, and the background corrected antigen stimulated levels of EGF and macrophage inflammatory protein (MIP)-1beta were the most informative single markers for differentiation between TB disease and LTBI, with AUCs of 0.88, 0.84, 0.87, 0.90 and 0.79 respectively. The combination of EGF and MIP-1beta predicted 96% of active TB cases and 92% of LTBIs. Combinations between EGF, sCD40L, VEGF, TGF-alpha and IL-1alpha also showed potential to differentiate between TB infection states. EGF, VEGF, TGF-alpha and sCD40L levels were higher in TB patients.
  
  
  CONCLUSIONS
  These preliminary data suggest that active TB may be accurately differentiated from LTBI utilizing adaptations of the commercial QFT test that includes measurement of EGF, sCD40L, MIP-1beta, VEGF, TGF-alpha or IL-1alpha in supernatants from QFT assays. This approach holds promise for development as a rapid diagnostic test for active TB.
authors.affiliation: Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Health Sciences, University of Stellenbosch, Cape Town, Western Cape Province, Tygerberg 7505, South Africa. novel@sun.ac.za
authors.forename: Novel N
authors.initials: NN
authors.lastname: Chegou
authors.forename: Gillian F
authors.initials: GF
authors.lastname: Black
authors.forename: Martin
authors.initials: M
authors.lastname: Kidd
authors.forename: Paul D
authors.initials: PD
authors.lastname: van Helden
authors.forename: Gerhard
authors.initials: G
authors.lastname: Walzl
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D023201:CD40 Ligand / Q000097:blood; D016358:Contact Tracing / Q000379:methods*; D004815:Epidermal Growth Factor / Q000097:blood; D005260:Female; D006801:Humans; D015994:Incidence; D007371:Interferon-gamma / Q000097:blood; D053582:Interleukin-1alpha / Q000097:blood; D008297:Male; D008828:Microbiological Techniques / Q000379:methods*; D008875:Middle Aged; D010865:Pilot Projects; D011933:Reagent Kits, Diagnostic; D013019:South Africa / Q000453:epidemiology; D016211:Transforming Growth Factor alpha / Q000097:blood; D014397:Tuberculosis, Pulmonary / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D015415:Biomarkers; D053582:Interleukin-1alpha; D011933:Reagent Kits, Diagnostic; D016211:Transforming Growth Factor alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D023201:CD40 Ligand; D004815:Epidermal Growth Factor; D007371:Interferon-gamma