title: A Mycobacterium tuberculosis Dormancy Antigen Differentiates Latently Infected Bacillus Calmette-Guérin-vaccinated Individuals.
abstract: IFN-γ release assays (IGRAs) are better indicators of Mycobacterium tuberculosis infection than the tuberculin skin test (TST) in Bacillus Calmette-Guérin (BCG)-vaccinated populations. However, IGRAs do not discriminate active and latent infections (LTBI) and no gold standard for LTBI diagnosis is available. Thus, since improved tests to diagnose M. tuberculosis infection are required, we assessed the efficacy of several M. tuberculosis latency antigens. BCG-vaccinated healthy donors (HD) and tuberculosis (TB) patients were recruited. QuantiFERON-TB Gold In-Tube, TST and clinical data were used to differentiate LTBI. IFN-γ production against CFP-10, ESAT-6, Rv2624c, Rv2626c and Rv2628 antigens was tested in peripheral blood mononuclear cells. LTBI subjects secreted significantly higher IFN-γ levels against Rv2626c than HD. Additionally, Rv2626c peptide pools to which only LTBI responded were identified, and their cumulative IFN-γ response improved LTBI discrimination. Interestingly, whole blood stimulation with Rv2626c allowed the discrimination between active and latent infections, since TB patients did not secrete IFN-γ against Rv2626c, in contrast to CFP-10 + ESAT-6 stimulation that induced IFN-γ response from both LTBI and TB patients. ROC analysis confirmed that Rv2626c discriminated LTBI from HD and TB patients. Therefore, since only LTBI recognizes specific epitopes from Rv2626c, this antigen could improve LTBI diagnosis, even in BCG-vaccinated people.
authors.affiliation: Instituto de Química Biológica, Facultad de Ciencias Exactas y Naturales (IQUIBICEN), UBA (Universidad de Buenos Aires)-CONICET, Intendente Güiraldes 2160, Pabellón II, 4°piso, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina ; Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, UBA, Intendente Güiraldes 2160, Pabellón II, 4°piso, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina.
authors.forename: Delfina
authors.initials: D
authors.lastname: Peña
authors.affiliation: Instituto de Química Biológica, Facultad de Ciencias Exactas y Naturales (IQUIBICEN), UBA (Universidad de Buenos Aires)-CONICET, Intendente Güiraldes 2160, Pabellón II, 4°piso, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina ; Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, UBA, Intendente Güiraldes 2160, Pabellón II, 4°piso, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Rovetta
authors.affiliation: Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, UBA, Intendente Güiraldes 2160, Pabellón II, 4°piso, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina.
authors.forename: Rodrigo E
authors.initials: RE
authors.lastname: Hernández Del Pino
authors.affiliation: Instituto de Química Biológica, Facultad de Ciencias Exactas y Naturales (IQUIBICEN), UBA (Universidad de Buenos Aires)-CONICET, Intendente Güiraldes 2160, Pabellón II, 4°piso, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina ; Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, UBA, Intendente Güiraldes 2160, Pabellón II, 4°piso, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina.
authors.forename: Nicolás O
authors.initials: NO
authors.lastname: Amiano
authors.affiliation: Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, UBA, Intendente Güiraldes 2160, Pabellón II, 4°piso, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina.
authors.forename: Virginia
authors.initials: V
authors.lastname: Pasquinelli
authors.affiliation: Instituto de Química Biológica, Facultad de Ciencias Exactas y Naturales (IQUIBICEN), UBA (Universidad de Buenos Aires)-CONICET, Intendente Güiraldes 2160, Pabellón II, 4°piso, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina ; Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, UBA, Intendente Güiraldes 2160, Pabellón II, 4°piso, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina.
authors.forename: Joaquín M
authors.initials: JM
authors.lastname: Pellegrini
authors.affiliation: Instituto de Química Biológica, Facultad de Ciencias Exactas y Naturales (IQUIBICEN), UBA (Universidad de Buenos Aires)-CONICET, Intendente Güiraldes 2160, Pabellón II, 4°piso, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina ; Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, UBA, Intendente Güiraldes 2160, Pabellón II, 4°piso, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Tateosian
authors.affiliation: Instituto de Química Biológica, Facultad de Ciencias Exactas y Naturales (IQUIBICEN), UBA (Universidad de Buenos Aires)-CONICET, Intendente Güiraldes 2160, Pabellón II, 4°piso, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina ; Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, UBA, Intendente Güiraldes 2160, Pabellón II, 4°piso, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina.
authors.forename: Agustín
authors.initials: A
authors.lastname: Rolandelli
authors.affiliation: Sección Bacteriología de la Tuberculosis, Hospital General de Agudos "Dr. E. Tornu", Combatientes de Malvinas 3002, 1427 Buenos Aires, Argentina.
authors.forename: Marisa
authors.initials: M
authors.lastname: Gutierrez
authors.affiliation: División Tisioneumonología Hospital F.J. Muñiz, Uspallata 2272, C1282AEN Buenos Aires, Argentina.
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Musella
authors.affiliation: División Tisioneumonología Hospital F.J. Muñiz, Uspallata 2272, C1282AEN Buenos Aires, Argentina.
authors.forename: Domingo J
authors.initials: DJ
authors.lastname: Palmero
authors.affiliation: INBIRS, Facultad de Medicina, UBA, Paraguay 2155, C1121ABG Buenos Aires, Argentina.
authors.forename: María M
authors.initials: MM
authors.lastname: Gherardi
authors.affiliation: Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, Marseille, France.
authors.forename: Juan
authors.initials: J
authors.lastname: Iovanna
authors.affiliation: Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Facultad de Medicina, UBA, Paraguay 2155, C1121ABG Buenos Aires, Argentina.
authors.forename: H Eduardo
authors.initials: HE
authors.lastname: Chuluyan
authors.affiliation: Instituto de Química Biológica, Facultad de Ciencias Exactas y Naturales (IQUIBICEN), UBA (Universidad de Buenos Aires)-CONICET, Intendente Güiraldes 2160, Pabellón II, 4°piso, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina ; Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, UBA, Intendente Güiraldes 2160, Pabellón II, 4°piso, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina.
authors.forename: Verónica E
authors.initials: VE
authors.lastname: García
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009163:Mycobacterium bovis / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage* / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; C573415:IFNG protein, human; D032581:Tuberculosis Vaccines; D007371:Interferon-gamma
keywords: Active tuberculosis; Antigens; Diagnosis; IFN-gamma; Latent tuberculosis