title: Immunogenicity of 60 novel latency-related antigens of Mycobacterium tuberculosis.
abstract: The aim of our work here was to evaluate the immunogenicity of 60 mycobacterial antigens, some of which have not been previously assessed, notably a novel series of in vivo-expressed Mycobacterium tuberculosis (IVE-TB) antigens. We enrolled 505 subjects and separated them in individuals with and without latent tuberculosis infection (LTBI) vs. patients with active tuberculosis (TB). Following an overnight and 7 days stimulation of whole blood with purified recombinant M. tuberculosis antigens, interferon-γ (IFN-γ) levels were determined by ELISA. Several antigens could statistically significantly differentiate the groups of individuals. We obtained promising antigens from all studied antigen groups [dormancy survival regulon (DosR regulon) encoded antigens; resuscitation-promoting factors (Rpf) antigens; IVE-TB antigens; reactivation associated antigens]. Rv1733, which is a probable conserved transmembrane protein encoded in DosR regulon, turned out to be very immunogenic and able to discriminate between the three defined TB status, thus considered a candidate biomarker. Rv2389 and Rv2435n, belonging to Rpf family and IVE-TB group of antigens, respectively, also stood out as LTBI biomarkers. Although more studies are needed to support our findings, the combined use of these antigens would be an interesting approach to TB immunodiagnosis candidates.
authors.affiliation: Department of Microbiology, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Hospital Universitari Germans Trias i Pujol Badalona, Spain ; Department of Genetics and Microbiology, Universitat Autònoma de Barcelona Bellaterra, Spain ; CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III Badalona, Spain.
authors.forename: Mᵃdel Mar
authors.initials: MM
authors.lastname: Serra-Vidal
authors.affiliation: Department of Microbiology, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Hospital Universitari Germans Trias i Pujol Badalona, Spain ; Department of Genetics and Microbiology, Universitat Autònoma de Barcelona Bellaterra, Spain ; CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III Badalona, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Latorre
authors.affiliation: Department of Immunohematology and Blood Transfusion/Department of Infectious Diseases, Leiden University Medical Center Leiden, Netherlands.
authors.forename: Kees L C M
authors.initials: KL
authors.lastname: Franken
authors.affiliation: Department of Microbiology, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Hospital Universitari Germans Trias i Pujol Badalona, Spain ; Department of Genetics and Microbiology, Universitat Autònoma de Barcelona Bellaterra, Spain ; CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III Badalona, Spain.
authors.forename: Jéssica
authors.initials: J
authors.lastname: Díaz
authors.affiliation: Department of Genetics and Microbiology, Universitat Autònoma de Barcelona Bellaterra, Spain ; Unitat de Tuberculosi de Drassanes, Hospital Universitari Vall d'Hebron Barcelona, Spain.
authors.forename: Maria Luiza
authors.initials: ML
authors.lastname: de Souza-Galvão
authors.affiliation: Department of Genetics and Microbiology, Universitat Autònoma de Barcelona Bellaterra, Spain ; Department of Preventive Medicine, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Hospital Universitari Germans Trias i Pujol Badalona, Spain.
authors.forename: Irma
authors.initials: I
authors.lastname: Casas
authors.affiliation: Serveis Clínics de Barcelona Barcelona, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Maldonado
authors.affiliation: Unitat de Tuberculosi de Drassanes, Hospital Universitari Vall d'Hebron Barcelona, Spain.
authors.forename: Cèlia
authors.initials: C
authors.lastname: Milà
authors.affiliation: Unitat de Tuberculosi de Drassanes, Hospital Universitari Vall d'Hebron Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Solsona
authors.affiliation: Unitat de Tuberculosi de Drassanes, Hospital Universitari Vall d'Hebron Barcelona, Spain.
authors.forename: M Ángeles
authors.initials: MÁ
authors.lastname: Jimenez-Fuentes
authors.affiliation: Unitat de Tuberculosi de Drassanes, Hospital Universitari Vall d'Hebron Barcelona, Spain.
authors.forename: Neus
authors.initials: N
authors.lastname: Altet
authors.affiliation: Department of Microbiology, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Hospital Universitari Germans Trias i Pujol Badalona, Spain ; Department of Genetics and Microbiology, Universitat Autònoma de Barcelona Bellaterra, Spain ; CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III Badalona, Spain.
authors.forename: Alícia
authors.initials: A
authors.lastname: Lacoma
authors.affiliation: Department of Genetics and Microbiology, Universitat Autònoma de Barcelona Bellaterra, Spain ; CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III Badalona, Spain ; Department of Pneumology, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Hospital Universitari Germans Trias i Pujol Badalona, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Ruiz-Manzano
authors.affiliation: Department of Microbiology, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Hospital Universitari Germans Trias i Pujol Badalona, Spain ; Department of Genetics and Microbiology, Universitat Autònoma de Barcelona Bellaterra, Spain ; CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III Badalona, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Ausina
authors.affiliation: Department of Microbiology, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Hospital Universitari Germans Trias i Pujol Badalona, Spain ; Department of Genetics and Microbiology, Universitat Autònoma de Barcelona Bellaterra, Spain ; CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III Badalona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Prat
authors.affiliation: Department of Immunohematology and Blood Transfusion/Department of Infectious Diseases, Leiden University Medical Center Leiden, Netherlands.
authors.forename: Tom H M
authors.initials: TH
authors.lastname: Ottenhoff
authors.affiliation: Department of Microbiology, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Hospital Universitari Germans Trias i Pujol Badalona, Spain ; Department of Genetics and Microbiology, Universitat Autònoma de Barcelona Bellaterra, Spain ; CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III Badalona, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Domínguez
keywords: antigenic stimulation; immune response; interferon-γ; latent tuberculosis infection; tuberculosis