Close contact interferon-gamma response to the new PstS1(285–374):CPF10: a preliminary 1-year follow-up study

• Published in: BMC research notes Vol. 10; no. 1; p. 59
• Main Authors: de Araujo, Leonardo Silva, de Bárbara Moreira da Silva Lins, Nidai, Leung, Janaina Aparecida Medeiros, Mello, Fernanda Carvalho Queiroz, Saad, Maria Helena Féres
• Format: Journal Article
• Language: English
• Published: London BioMed Central 23.01.2017; BioMed Central Ltd
• Subjects: Adult; Antigens; Antigens, Bacterial - immunology; Biomedical and Life Sciences; Biomedicine; Care and treatment; Demography; Female; Follow-Up Studies; Genetic aspects; Humans; Immunology; Interferon gamma; Interferon-gamma - metabolism; Interferon-gamma Release Tests - methods; Latent Tuberculosis - diagnosis; Latent Tuberculosis - immunology; Latent Tuberculosis - microbiology; Latent Tuberculosis - prevention & control; Life Sciences; Male; Medicine/Public Health; Middle Aged; Mycobacterium tuberculosis - immunology; Research Article; Risk factors; Tuberculosis; Interferon-gamma; Follow up; Tuberculosis; LTBI; M. tuberculosis
• ISSN: 1756-0500; 1756-0500
• DOI: 10.1186/s13104-016-2360-4

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. Conclusion 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.