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

This article is published by Frontiers in Immunology.

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Main Authors: Adankwah Ernest, Lundtoft Christian, Owusu-Dabo Ellis, Franken L. M. C. Kees...et al
Format: Article
Language:English
Published: Frontiers In Immunology 2023
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access_status_str Open Access
author Adankwah Ernest
Lundtoft Christian
Owusu-Dabo Ellis
Franken L. M. C. Kees...et al
author_browse Adankwah Ernest
Franken L. M. C. Kees...et al
Lundtoft Christian
Owusu-Dabo Ellis
author_facet Adankwah Ernest
Lundtoft Christian
Owusu-Dabo Ellis
Franken L. M. C. Kees...et al
author_sort Adankwah Ernest
collection Thesis
description This article is published by Frontiers in Immunology.
format Article
id oai:ir.knust.edu.gh:123456789/14690
institution KNUST (Ghana)
language English
last_indexed 2026-07-01T04:00:52.249Z
license_str Not specified — see source repository
provenance_str_mv Harvested via OAI-PMH from KNUSTSpace — Kwame Nkrumah University of Science & Technology (Ghana)
publishDate 2023
publishDateRange 2023
publishDateSort 2023
publisher Frontiers In Immunology
publisherStr Frontiers In Immunology
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source_str KNUSTSpace — Kwame Nkrumah University of Science & Technology (Ghana)
spelling oai:ir.knust.edu.gh:123456789/14690 Two-Hit in vitro T-Cell Stimulation Detects Mycobacterium tuberculosis Infection in QuantiFERON Negative Tuberculosis Patients and Healthy Contacts From Ghana Adankwah Ernest Lundtoft Christian Owusu-Dabo Ellis Franken L. M. C. Kees...et al This article is published by Frontiers in Immunology. IFN-γ 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-γ 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-γ background values. Intracellular IFN-γ 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-γ 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-γ 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 KNUST 2023-12-06T16:46:46Z 2023-12-06T16:46:46Z 2019 Article Adankwah E, Lundtoft C, Güler A, Franken KLMC, Ottenhoff THM, Mayatepek E, Owusu-Dabo E, Phillips RO, Nausch N and Jacobsen M (2019) Two-Hit in vitro T-Cell Stimulation Detects Mycobacterium tuberculosis Infection in QuantiFERON Negative Tuberculosis Patients and Healthy Contacts From Ghana 10.3389/fimmu.2019.0151 https://ir.knust.edu.gh/handle/123456789/14690 en application/pdf Frontiers In Immunology
spellingShingle Adankwah Ernest
Lundtoft Christian
Owusu-Dabo Ellis
Franken L. M. C. Kees...et al
Two-Hit in vitro T-Cell Stimulation Detects Mycobacterium tuberculosis Infection in QuantiFERON Negative Tuberculosis Patients and Healthy Contacts From Ghana
title Two-Hit in vitro T-Cell Stimulation Detects Mycobacterium tuberculosis Infection in QuantiFERON Negative Tuberculosis Patients and Healthy Contacts From Ghana
title_full Two-Hit in vitro T-Cell Stimulation Detects Mycobacterium tuberculosis Infection in QuantiFERON Negative Tuberculosis Patients and Healthy Contacts From Ghana
title_fullStr Two-Hit in vitro T-Cell Stimulation Detects Mycobacterium tuberculosis Infection in QuantiFERON Negative Tuberculosis Patients and Healthy Contacts From Ghana
title_full_unstemmed Two-Hit in vitro T-Cell Stimulation Detects Mycobacterium tuberculosis Infection in QuantiFERON Negative Tuberculosis Patients and Healthy Contacts From Ghana
title_short Two-Hit in vitro T-Cell Stimulation Detects Mycobacterium tuberculosis Infection in QuantiFERON Negative Tuberculosis Patients and Healthy Contacts From Ghana
title_sort two hit in vitro t cell stimulation detects mycobacterium tuberculosis infection in quantiferon negative tuberculosis patients and healthy contacts from ghana
url https://ir.knust.edu.gh/handle/123456789/14690
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