title: Improving T-cell assays for diagnosis of latent TB infection: Confirmation of the potential role of testing Interleukin-2 release in Iranian patients.
abstract: BACKGROUND
  Since gamma interferon release assays (IGRAs) cannot differentiate between active tuberculosis and latent tuberculosis infection (LTBI), development of rapid and specific diagnosis tools are essential for discriminating between active tuberculosis (TB) from LTBI. Both IGRAs are based on Mycobacterium tuberculosis-specific antigens, namely, early secretory antigenic target 6 (ESAT-6) and 10kDa culture filtrate (CFP-10). The aim of this study was to evaluate the potential value of IL-2 secretion by whole blood cells after stimulation with rESAT-6 and rCFP-10 for discriminating between active and latent tuberculosis.
  
  
  METHODS
  Interleukin-2 and IFN-γ were measured after blood stimulation of 90 cases (30 with active TB, 30 with LTBI and 30 healthy controls) with recombinant ESAT-6 and CFP-10. Receiver operating characteristic (ROC) curve analysis was conducted to determine the best IL-2 and IFN-γ result thresholds in discriminating between cases with active or latent TB, and the corresponding sensitivity and specificity were recorded.
  
  
  RESULTS
  The IFN-γ release assay demonstrated a good sensitivity and specificity (sensitivity 83-84% and specificity 92%) for diagnosis of tuberculosis. The discrimination performance of IL-2 assay (assessed by the area under ROC curve) between LTBI and patients with active TB were 0.75 and 0.8 following stimulation with rESAT-6 and rCFP-10, respectively. Maximum discrimination was reached at a cut-off of 11.6pg/mL for IL-2 after stimulation with recombinant rESAT-6 with 72% sensitivity and 79% specificity and 10.7pg/mL for IL-2 following stimulation with rCFP-10 with 75% sensitivity and 79% specificity, respectively.
  
  
  CONCLUSIONS
  This study demonstrates that rESAT-6 and rCFP-10 can provide a sensitive and specific diagnosis of TB. In addition, it was shown that IL-2 may be serving as a marker for discriminating LTBI and active TB.
authors.affiliation: Pediatric Infectious Disease Research Center, Tehran University of Medical Science, Tehran, Iran; Department of Infectious Diseases, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: S
authors.initials: S
authors.lastname: Mamishi
authors.affiliation: Pediatric Infectious Disease Research Center, Tehran University of Medical Science, Tehran, Iran.
authors.forename: B
authors.initials: B
authors.lastname: Pourakbari
authors.affiliation: Center for Pulmonary and Infectious Disease Control, and Departments of Microbiology and Immunology and Medicine, University of Texas Health Center at Tyler, Tyler, TX, USA.
authors.forename: H
authors.initials: H
authors.lastname: Shams
authors.affiliation: Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Marjani
authors.affiliation: Pediatric Infectious Disease Research Center, Tehran University of Medical Science, Tehran, Iran. Electronic address: sh-mahmoudi@alumnus.tums.ac.ir.
authors.forename: S
authors.initials: S
authors.lastname: Mahmoudi
mesh_terms: D000293:Adolescent; D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D059425:Interferon-gamma Release Tests / Q000379:methods*; D007376:Interleukin-2 / Q000097:blood*; D007492:Iran; D055985:Latent Tuberculosis / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D011994:Recombinant Proteins / Q000276:immunology; D012680:Sensitivity and Specificity; D013601:T-Lymphocytes / Q000276:immunology*; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D015415:Biomarkers; C117940:CFP-10 protein, Mycobacterium tuberculosis; C093276:ESAT-6 protein, Mycobacterium tuberculosis; C508594:IL2 protein, human; D007376:Interleukin-2; D011994:Recombinant Proteins; C072681:Mycobacterium tuberculosis antigens; D007371:Interferon-gamma
keywords: Active TB; Discrimination; IL-2; LTBI