title: Close contact interferon-gamma response to the new PstS1(285-374):CPF10: a preliminary 1-year follow-up study.
abstract: BACKGROUND
  The available diagnostic tools for latent tuberculosis (TB) infection (LTBI) via interferon-gamma (IFN-g) release assays (IGRA) are based on ESAT6:CFP10 stimulation. However, the mycobacterial antigen PstS1 is also highly immunogenic and some of its fragments, such as PstS1(285-374), have shown higher immunoreactivity in LTBI than in active TB. PstS1(285-374), therefore, could increase the accuracy of the existing IGRA to detect LTBI. Thus, a new chimeric protein has recently been developed (PstS1(285-374):CFP10) showing potential for LTBI screening of recent close contacts (rCt) exposed to Mycobacterium tuberculosis. The aim of this study was to analyze the PstS1(285-374):CFP10 longitudinal IFN-g profile in comparison to ESAT6:CFP10 and full PstS1/CFP10 stimulation in a rCt cohort and correlate the responses to these in-house IGRA with any clinical changes/interventions that might occur.
  
  
  METHODS
  A free-of-cost, one-year follow up was offered to 120 rCt recruited in Rio de Janeiro, RJ, Brazil. Whole blood short-term (WBA), long-term stimulation (LSA) assays, and the tuberculin skin test (TST) were performed during follow up.
  
  
  RESULTS
  Among the enrolled rCt, 44.2% (53/120) returned for re-evaluation and the control group (TST negative, n = 17) showed low IFN-g reactivity to all antigen stimulations during the entire follow up, except for one participant who had shown radiological evidence of past TB/LTBI. Both incident cases were detected by IGRA-PstS1(285-374):CFP10 during LTBI and after disease progression. Moreover, subsequent to the prophylactic treatment for LTBI (tLTBI), a significant regression in the LSA response was predominantly observed through stimulation of the new chimeric protein (8/10, 80%) followed by ESAT6:CFP10 (5/10, 50%) and PstS1/CFP10 (4/10, 40%). No clinical or epidemiological characteristics were exclusively shared among IGRA convertors.
  
  
  CONCLUSIONS
  It was demonstrated that the TST negative rCt without radiological evidence of LTBI/TB did not develop an IGRA-PstS1(285-374):CFP10 response during the one-year follow up. Moreover, all incident cases were detected by our new IGRA; and a significant decrement of LSA-PstS1(285-374):CFP10 reactivity post-prophylactic tLTBI was found. To our knowledge, this is the first study to monitor changes in the immune response profile of IGRA-PstS1(285-374):CFP10 among rCt during a consecutive one-year period, thus providing additional evidence of its potential in the detection of LTBI.
authors.affiliation: Laboratory of Cellular Microbiology, Oswaldo Cruz Institute, Fiocruz, Avenida Brasil, 4365, Rio de Janeiro, RJ, 20045-360, Brazil.
authors.forename: Leonardo Silva
authors.initials: LS
authors.lastname: de Araujo
authors.affiliation: Laboratory of Cellular Microbiology, Oswaldo Cruz Institute, Fiocruz, Avenida Brasil, 4365, Rio de Janeiro, RJ, 20045-360, Brazil.
authors.forename: Nidai
authors.initials: N
authors.lastname: de Bárbara Moreira da Silva Lins
authors.affiliation: Federal University of Rio de Janeiro, Helio Fraga Filho Hospital, Professor Rodolpho Paulo Rocco Street, 255, 1st Floor, Ilha do Fundão, Rio de Janeiro, RJ, 21941-913, Brazil.
authors.forename: Janaina Aparecida Medeiros
authors.initials: JA
authors.lastname: Leung
authors.affiliation: Federal University of Rio de Janeiro, Helio Fraga Filho Hospital, Professor Rodolpho Paulo Rocco Street, 255, 1st Floor, Ilha do Fundão, Rio de Janeiro, RJ, 21941-913, Brazil.
authors.forename: Fernanda Carvalho Queiroz
authors.initials: FC
authors.lastname: Mello
authors.affiliation: Laboratory of Cellular Microbiology, Oswaldo Cruz Institute, Fiocruz, Avenida Brasil, 4365, Rio de Janeiro, RJ, 20045-360, Brazil. saad@ioc.fiocruz.br.
authors.forename: Maria Helena Féres
authors.initials: MH
authors.lastname: Saad
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology*; D003710:Demography; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D059425:Interferon-gamma Release Tests / Q000379:methods*; D055985:Latent Tuberculosis / Q000175:diagnosis* / Q000276:immunology / Q000382:microbiology* / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D007371:Interferon-gamma
keywords: Follow up; Interferon-gamma; LTBI; M. tuberculosis; Tuberculosis