title: Novel T-cell assays for the discrimination of active and latent tuberculosis infection: the diagnostic value of PPE family.
abstract: OBJECTIVE
  The diagnosis of active and latent tuberculosis remains a challenge. Although a new approach based on detecting Mycobacterium tuberculosis-specific T-cells has been introduced, it cannot distinguish between latent infection and active disease. The aim of this study was to evaluate the diagnostic potential of interleukin-2 (IL-2) as biomarker after specific antigen stimulation with PE35 and PPE68 for the discrimination of active and latent tuberculosis infection (LTBI).
  
  
  METHODS
  The production of IL-2 was measured in the antigen-stimulated whole-blood supernatants following stimulation with recombinant PE35 and PPE68.
  
  
  RESULTS
  The discrimination performance (assessed by the area under ROC curve) for IL-2 following stimulation with recombinant PE35 and PPE68 between LTBI and patients with active TB were 0.837 [95 % confidence interval (CI) 0.72-0.97] for LTBI diagnosis and 0.75 (95 % CI 0.63-0.89) for active TB diagnosis, respectively. Applying the 6.4 pg/mL cut-off for IL-2 induced by PE35 in the present study population resulted in sensitivity of 78 %, specificity of 83 %, PPV of 83 % and NPV of 78 % for the discrimination of active TB and LTBI. In addition, a sensitivity of 81 %, specificity of 71 %, PPV of 68 and 83 % of NPV was reported based on the 4.4 pg/mL cut-off for IL-2 induced by PPE68.
  
  
  CONCLUSIONS
  This study confirms IL-2 induced by PE35 and PPE68 as a sensitive and specific biomarker and highlights IL-2 as new promising adjunct markers for discriminating of LTBI and active TB disease.
authors.affiliation: Pediatric Infectious Disease Research Center, Tehran University of Medical Sciences, Children's Medical Center Hospital, Dr. Gharib Street, Keshavarz Boulevard, Tehran, Iran.
authors.forename: Babak
authors.initials: B
authors.lastname: Pourakbari
authors.affiliation: Pediatric Infectious Disease Research Center, Tehran University of Medical Sciences, Children's Medical Center Hospital, Dr. Gharib Street, Keshavarz Boulevard, Tehran, Iran.|Department of Infectious Diseases, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Setareh
authors.initials: S
authors.lastname: Mamishi
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: Majid
authors.initials: M
authors.lastname: Marjani
authors.affiliation: Department of Infectious Diseases, Imam Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mehrnaz
authors.initials: M
authors.lastname: Rasulinejad
authors.affiliation: Dipartimento di Malattie Infettive, Parassitarie e Immunomediate Istituto Superiore di Sanita', Roma, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Mariotti
authors.affiliation: Pediatric Infectious Disease Research Center, Tehran University of Medical Sciences, Children's Medical Center Hospital, Dr. Gharib Street, Keshavarz Boulevard, Tehran, Iran. sh-mahmoudi@alumnus.tums.ac.ir.
authors.forename: Shima
authors.initials: S
authors.lastname: Mahmoudi
mesh_terms: D000293:Adolescent; D000328:Adult; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000097:blood*; D055985:Latent Tuberculosis / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology; D012680:Sensitivity and Specificity; D013601:T-Lymphocytes / Q000276:immunology*; D055815:Young Adult
chemical_list: D001426:Bacterial Proteins; D015415:Biomarkers; D007376:Interleukin-2; C528814:PPE68 protein, Mycobacterium tuberculosis