Abstract
Interferon gamma (IFN-γ) release assays (IGRAs) detect Mycobacterium tuberculosis (Mtb) infection regardless of the active (ATB) or latent (LTBI) forms of tuberculosis (TB). In this study, Mtb-specific T cell response against region of deletion 1 (RD1) antigens were explored by a microbead multiplex assay performed in T-SPOT TB assay (T-SPOT) supernatants from 35 patients with ATB and 115 patients with LTBI. T-SPOT is positive when over 7 IFN-γ secreting cells (SC)/250 000 peripheral blood mononuclear cells (PBMC) are enumerated. However, over 100 IFN-γ SC /250 000 PBMC were more frequently observed in the ATB group compared to the LTBI group. By contrast, lower cytokine concentrations and lower cytokine productions relative to IFN-γ secretion were observed for IL 4, IL-12, TNF-α, GM-CSF, Eotaxin and IFN-α when compared to LTBI. Thus, high IFN-γ release and low cytokine secretions in relation with IFN-γ production appeared as signatures of ATB, corroborating that multicytokine Mtb-specific response against RD1 antigens reflects host capacity to contain TB reactivation. In this way, testing cytokine profile in IGRA supernatants would be helpful to improve ATB screening strategy including immunologic tests.
Highlights
Almost one third of the world population is infected by Mycobacterium tuberculosis (Mtb)
We reported that evaluation of IL-2, IL-15, IP-10 and MIG) may be useful to detect latent tuberculosis infection (LTBI) in healthcare workers exposed to TB and tested positive by TST but negative by Interferon gamma (IFN-γ) release assays (IGRAs) [11]
T cell signature associated with active disease and latent forms of Mtb infection was characterized using a commercial IGRA, the T-SPOT assay, and cytokine analysis with a microbead multiplex assay to simultaneously measure multiple immune mediators in the cell culture supernatants
Summary
Almost one third of the world population is infected by Mycobacterium tuberculosis (Mtb). Most of the infected individuals will remain asymptomatic, but 10% will develop active tuberculosis (ATB) disease during lifetime leading to death if left untreated [1]. There is no diagnostic gold standard for latent tuberculosis infection (LTBI). T Cell Signature Associated with Active Tuberculosis manuscript. The Fondation de France provided support in the form of salaries for SCK
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