title: Modulation of interferon-gamma response to QuantiFERON-TB-plus detected by enzyme-linked immunosorbent assay in patients with active and latent tuberculosis infection.
abstract: OBJECTIVE
  Interferon (IFN)-γ-release assays (IGRAs) are designed for the diagnosis of tuberculosis (TB) infection. The new IGRA called QuantiFERON-TB Plus (QFT-Plus) is based on enzyme-linked immunosorbent assay (ELISA) detection of IFN-γ following Myobacterium tuberculosis-antigen stimulation with TB1 and TB2 antigens. TB1 elicits a cell-mediated immune response by CD4 T cells and TB2 elicits a response from both CD4 and CD8 T cells. Here, we characterized variations IFN-γ release detected by ELISA to QFT-IT and QFT-Plus in patients with active TB and latent TB infection (LTBI) at baseline and during or after specific treatment (follow-up).
  
  
  METHODS
  We studied seven patients with active TB and 10 patients with LTBI at baseline and during treatment either for active disease or preventive therapy. IFN-γ release detected by ELISA to QFT-IT and QFT-Plus was concomitantly evaluated over time. Statistical analysis was performed using a nonparametrical test for a paired dataset (Wilcoxon test).
  
  
  RESULTS
  All participants responded to the mitogen, with all active-TB patients responding to QFT-IT or QFT-Plus at baseline. The responses did not change over time either qualitatively (number of responders) or quantitatively (IFN-γ release evaluated as IU/mL). Among the LTBI group, although all participants responded to both QFT-IT and QFT-Plus and the responses did not change over time, the quantitative responses to QFT-Plus showed a different trend. Specifically, response to TB2 was significantly lower at follow-up as compared with that observed at baseline (p=0.004), whereas the response to TB1 was not significantly different (p=0.16).
  
  
  CONCLUSIONS
  To our knowledge, this is the first report characterizing IFN-γ responses to QFT-Plus antigens in participants with active TB and LTBI over time. The data need to be confirmed in larger settings; however, we showed that monitoring IFN-γ release in response to TB2 can be used to evaluate preventive therapy immune changes. This can be useful also as a tool for public health control strategies in settings where preventive treatment is recommended.
authors.affiliation: Translational Research Unit, Department of Epidemiology and Preclinical Research, National Institute for Infectious Diseases (INMI) "L. Spallanzani", Rome, Italy. Electronic address: elisa.petruccioli@inmi.it.
authors.forename: Elisa
authors.initials: E
authors.lastname: Petruccioli
authors.affiliation: Translational Research Unit, Department of Epidemiology and Preclinical Research, National Institute for Infectious Diseases (INMI) "L. Spallanzani", Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Vanini
authors.affiliation: Translational Research Unit, Department of Epidemiology and Preclinical Research, National Institute for Infectious Diseases (INMI) "L. Spallanzani", Rome, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Chiacchio
authors.affiliation: Emerging Bacterial Pathogens Unit, Division of Immunology and Infectious Diseases IRCCS, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Daniela M
authors.initials: DM
authors.lastname: Cirillo
authors.affiliation: Department of Clinical and Clinical Research, National Institute for Infectious Diseases (INMI), Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Palmieri
authors.affiliation: Scientific Direction, National Institute for Infectious Diseases (INMI), Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ippolito
authors.affiliation: Translational Research Unit, Department of Epidemiology and Preclinical Research, National Institute for Infectious Diseases (INMI) "L. Spallanzani", Rome, Italy.
authors.forename: Delia
authors.initials: D
authors.lastname: Goletti
keywords: Diagnosis; Infection; Latency; Quantiferon-Plus; Tuberculosis