Two-Hit in vitro T-Cell Stimulation Detects Mycobacterium tuberculosis Infection in QuantiFERON Negative Tuberculosis Patients and Healthy Contacts From Ghana

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dc.contributor.authorPhillips, Richard O.
dc.contributor.authorAdankwah, Ernest
dc.contributor.authorLundtoft, Christian
dc.contributor.authorGüler, Alptekin
dc.contributor.authorL. M. C, Kees
dc.contributor.authoret. al
dc.date.accessioned2020-01-13T13:10:55Z
dc.date.accessioned2023-04-19T01:48:31Z
dc.date.available2020-01-13T13:10:55Z
dc.date.available2023-04-19T01:48:31Z
dc.date.issued2019-07-03
dc.descriptionAn article published by Frontiers in Immunology and available at doi: 10.3389/fimmu.2019.01518en_US
dc.description.abstractIFN-g release assays [e.g., QuantiFERON (QFT)] are widely used for diagnosis of Mycobacterium tuberculosis (Mtb) infection. T-cell responses against QFT antigens ESAT6 and CFP10 are highly Mtb specific but previous studies indicated suboptimal assay sensitivity. Especially for potentially infected healthy contacts (HCs) of tuberculosis patients, alternative antigen usage and more sensitive tests may contribute to improved detection of latent Mtb infection. In a pilot case-control study of tuberculosis patients (n = 22) and HCs (n = 20) from Ghana, we performed multifaceted in vitro assays to identify optimal assay conditions. This included a two-hit stimulation assay, which is based on initial and second re-stimulation with the same antigen on d6 and intracellular IFN-g analysis, to compare T-cell responses against ESAT6/CFP10 (E6/C10) and selected latency antigens (i.e. Rv2628, Rv1733, Rv2031, Rv3407) of Mtb. Considerable subgroups of tuberculosis patients (64%) and HCs (75%) had negative or indeterminate QFT results partially accompanied by moderate PHA induced responses and high IFN-g background values. Intracellular IFN-g analysis of E6/C10 specific CD4+ T-cell subpopulations and evaluation of responder frequencies had only moderate effects on assay sensitivity. However, two-hit in vitro stimulation significantly enhanced E6/C10 specific IFN-g positive T-cell proportions especially in QFT non-responders, and in both study groups. Mtb latency antigen-specific T cells against Rv1733 and Rv2628 were especially detected in HCs after two-hit stimulation and T-cell responses against Rv2628 were highly capable to discriminate tuberculosis patients and HCs. Two-hit in vitro stimulation may improve moderate sensitivity of short term IFN-g based assays, like QFT, to detect Mtb infection. Latency stage-specific antigens added significantly to detection of Mtb infection in HCs and tuberculosis patients with negative QFT test results.en_US
dc.description.sponsorshipKNUSTen_US
dc.identifier.citationFront. Immunol. 10:1518. doi: 10.3389/fimmu.2019.01518en_US
dc.identifier.urihttps://ir.knust.edu.gh/handle/123456789/11924
dc.language.isoenen_US
dc.publisherFrontiers in Immunologyen_US
dc.subjecttuberculosisen_US
dc.subjectLTBIen_US
dc.subjectIGRAen_US
dc.subjectMycobacterium tuberculosis latency antigens,en_US
dc.subjectESAT6en_US
dc.subjectCFP10en_US
dc.titleTwo-Hit in vitro T-Cell Stimulation Detects Mycobacterium tuberculosis Infection in QuantiFERON Negative Tuberculosis Patients and Healthy Contacts From Ghanaen_US
dc.typeArticleen_US
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