title: Combination of cytokine responses indicative of latent TB and active TB in Malawian adults.
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.
authors.affiliation: Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom.
authors.forename: Yun-Gyoung
authors.initials: YG
authors.lastname: Hur
authors.forename: Patricia
authors.initials: P
authors.lastname: Gorak-Stolinska
authors.forename: Anne
authors.initials: A
authors.lastname: Ben-Smith
authors.forename: Maeve K
authors.initials: MK
authors.lastname: Lalor
authors.forename: Steven
authors.initials: S
authors.lastname: Chaguluka
authors.forename: Russell
authors.initials: R
authors.lastname: Dacombe
authors.forename: T Mark
authors.initials: TM
authors.lastname: Doherty
authors.forename: Tom H
authors.initials: TH
authors.lastname: Ottenhoff
authors.forename: Hazel M
authors.initials: HM
authors.lastname: Dockrell
authors.forename: Amelia C
authors.initials: AC
authors.lastname: Crampin
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D054357:Chemokine CXCL10 / Q000276:immunology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007378:Interleukins / Q000276:immunology; D055985:Latent Tuberculosis / Q000175:diagnosis* / Q000276:immunology*; D008295:Malawi; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology; D011446:Prospective Studies; D013183:Sputum / Q000276:immunology; D014373:Tuberculin / Q000276:immunology; D014374:Tuberculin Test / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D007378:Interleukins; D014373:Tuberculin; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma