title: Profile of interferon-gamma response to latency-associated and novel in vivo expressed antigens in a cohort of subjects recently exposed to Mycobacterium tuberculosis.
abstract: Recently some latency-associated antigens (LAA) of Mycobacterium tuberculosis were described, as Rv2029c, Rv2031c, Rv2034, Rv2628 and Rv3353c. Of which, the Rv2034 and Rv3353c also demonstrated in vivo expression. Therefore evaluating the immune response to these antigens may help to understand their role in latent TB infection. In a 1-year longitudinal study, IFN-γ response by in vitro peripheral blood mononuclear cells stimulation with LAA was investigated in subjects recently exposed to TB, classified by IFN-γ release assay (IGRA) using RD1 antigens (ESAT-6:CFP-10) and tuberculin skin test (TST) response. Except for Rv3353c, all the LAA triggered higher mean IFN-γ response in IGRA-RD1(+) groups (p < 0.05). Combining the IFN-γ-responders to Rv2029c, Rv2031c plus Rv2034 detected 90.3% (28/31) of IGRA-RD1(+) and 66.7% (24/36) of TST(+) contacts, while 95% (19/20) and 11% (2/17) were identified by classifying them according to a TST and IGRA-RD1 double-positive or double-negative response, respectively. In the follow-up, the TST convertors (negative to positive) also demonstrated an IFN-γ conversion to Rv2029c and Rv2031c, whereas the unique TB incident case was exclusively detected via IGRA-Rv2029c and TST before developing TB. A reversion rate to LAA (60%-100%) after prophylactic treatment was observed at TST(+)/IGRA-RD1(+) group. Further studies into the performance of these antigens are thus warranted.
authors.affiliation: Laboratory of Cellular Microbiology, Oswaldo Cruz Institute, Fiocruz, Avenida Brasil, 4365, Rio de Janeiro, RJ 20045-360, Brazil. Electronic address: araujo.s.leonardo@gmail.com.
authors.forename: Leonardo Silva de
authors.initials: LS
authors.lastname: Araujo
authors.affiliation: Laboratory of Cellular Microbiology, Oswaldo Cruz Institute, Fiocruz, Avenida Brasil, 4365, Rio de Janeiro, RJ 20045-360, Brazil. Electronic address: nidai2@hotmail.com.
authors.forename: Nidai de Bárbara Moreira
authors.initials: NBM
authors.lastname: da Silva
authors.affiliation: Laboratory of Cellular Microbiology, Oswaldo Cruz Institute, Fiocruz, Avenida Brasil, 4365, Rio de Janeiro, RJ 20045-360, Brazil. Electronic address: renanjeremias@hotmail.com.
authors.forename: Renan Jeremias
authors.initials: RJ
authors.lastname: da Silva
authors.affiliation: Federal University of Rio de Janeiro, Helio Fraga Filho Hospital, Av. Professor Rodolpho Paulo Rocco, 255, 1st Floor, Ilha do Fundão, Rio de Janeiro, RJ 21941-913, Brazil. Electronic address: janainaleung@hucff.ufrj.br.
authors.forename: Janaina Aparecida Medeiros
authors.initials: JAM
authors.lastname: Leung
authors.affiliation: Federal University of Rio de Janeiro, Helio Fraga Filho Hospital, Av. Professor Rodolpho Paulo Rocco, 255, 1st Floor, Ilha do Fundão, Rio de Janeiro, RJ 21941-913, Brazil. Electronic address: fcqmello@uninet.com.br.
authors.forename: Fernanda Carvalho Queiroz
authors.initials: FCQ
authors.lastname: Mello
authors.affiliation: Laboratory of Cellular Microbiology, Oswaldo Cruz Institute, Fiocruz, Avenida Brasil, 4365, Rio de Janeiro, RJ 20045-360, Brazil. Electronic address: saad@ioc.fiocruz.br.
authors.forename: Maria Helena Féres
authors.initials: MHF
authors.lastname: Saad
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology*; D059425:Interferon-gamma Release Tests; D055985:Latent Tuberculosis / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000382:microbiology; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D012097:Repressor Proteins / Q000276:immunology; D013997:Time Factors; D014374:Tuberculin Test
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D015415:Biomarkers; C118127:HspX protein, Mycobacterium tuberculosis; C573415:IFNG protein, human; D012097:Repressor Proteins; C000593589:Rv2034 protein, Mycobacterium tuberculosis; D007371:Interferon-gamma
keywords: Immune response; Interferon gamma; LTBI; Latency-associated antigens; Mycobacterium tuberculosis; Tuberculosis