title: Dominant TNF-α+ Mycobacterium tuberculosis-specific CD4+ T cell responses discriminate between latent infection and active disease.
abstract: Rapid diagnosis of active Mycobacterium tuberculosis (Mtb) infection remains a clinical and laboratory challenge. We have analyzed the cytokine profile (interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2)) of Mtb-specific T cells by polychromatic flow cytometry. We studied Mtb-specific CD4+ T cell responses in subjects with latent Mtb infection and active tuberculosis disease. The results showed substantial increase in the proportion of single-positive TNF-α Mtb-specific CD4+ T cells in subjects with active disease, and this parameter was the strongest predictor of diagnosis of active disease versus latent infection. We validated the use of this parameter in a cohort of 101 subjects with tuberculosis diagnosis unknown to the investigator. The sensitivity and specificity of the flow cytometry-based assay were 67% and 92%, respectively, the positive predictive value was 80% and the negative predictive value was 92.4%. Therefore, the proportion of single-positive TNF-α Mtb-specific CD4+ T cells is a new tool for the rapid diagnosis of active tuberculosis disease.
authors.affiliation: Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Harari
authors.forename: Virginie
authors.initials: V
authors.lastname: Rozot
authors.forename: Felicitas
authors.initials: F
authors.lastname: Bellutti Enders
authors.forename: Matthieu
authors.initials: M
authors.lastname: Perreau
authors.forename: Jesica Mazza
authors.initials: JM
authors.lastname: Stalder
authors.forename: Laurent P
authors.initials: LP
authors.lastname: Nicod
authors.forename: Matthias
authors.initials: M
authors.lastname: Cavassini
authors.forename: Thierry
authors.initials: T
authors.lastname: Calandra
authors.forename: Catherine Lazor
authors.initials: CL
authors.lastname: Blanchet
authors.forename: Katia
authors.initials: K
authors.lastname: Jaton
authors.forename: Mohamed
authors.initials: M
authors.lastname: Faouzi
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Day
authors.forename: Willem A
authors.initials: WA
authors.lastname: Hanekom
authors.forename: Pierre-Alexandre
authors.initials: PA
authors.lastname: Bart
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pantaleo
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D014409:Tumor Necrosis Factor-alpha