IGRAs--the gateway to T cell based TB diagnosis

Hilary S. Whitworth, Melanie Scott, David W Connell, Bianca Dongés, Ajit Lalvani (Lead / Corresponding author)

    Research output: Contribution to journalReview article

    40 Citations (Scopus)

    Abstract

    Development of Interferon-Gamma Release Assays (IGRAs) and implementation of their use in clinical practice almost 10 years ago has revolutionised diagnosis of latent tuberculosis (TB) infection (LTBI). The commercially available IGRAs, TSPOT.TB (Oxford Immunotech, Oxford, UK) and QuantiFERON Gold In-Tube (Cellestis, Victoria, Australia), allow detection of TB infection with greater specificity and sensitivity than the tuberculin skin test (TST) and are now recommended for diagnosis of LTBI. The TSPOT.TB assay is a simplified enzyme-linked immunospot assay (ELISpot) that enumerates TB-specific T lymphocytes (T cells) secreting interferon-gamma (IFNγ). In comparison, the QuantiFERON Gold In-Tube assay constitutes an enzyme-linked immunosorbent assay (ELISA) to quantify IFNγ released into blood plasma after incubation of whole blood with TB antigens. Release of IFNγ, as a result of antigen stimulation of TB-specific T cells within blood, is indicative of TB infection. Although IGRAs have significant advantages over the TST in diagnosis of latent TB, they have significant limitations. Discovery of new antigens and advances in methodology for measuring cellular immunity have recently paved the way for novel tests that overcome these limitations. By establishing for the first time technological platforms for T cell based diagnosis in diagnostic service laboratories, IGRAs provide a bridgehead to clinical application of T cell based diagnosis in routine practice.

    Original languageEnglish
    Pages (from-to)52-62
    Number of pages11
    JournalMethods (San Diego, Calif.)
    Volume61
    Issue number1
    DOIs
    Publication statusPublished - 15 May 2013

    Fingerprint

    Interferon-gamma Release Tests
    T-cells
    Interferon-gamma
    Assays
    Tuberculosis
    T-Lymphocytes
    Latent Tuberculosis
    Tuberculin Test
    Blood
    Skin Tests
    Antigens
    Tuberculin
    Gold
    Skin
    Diagnostic Services
    Enzyme-Linked Immunospot Assay
    Victoria
    Immunosorbents
    Infection
    Cellular Immunity

    Keywords

    • Antigens, Bacterial/immunology
    • Enzyme-Linked Immunosorbent Assay
    • Enzyme-Linked Immunospot Assay
    • Humans
    • Interferon-gamma/blood
    • Interferon-gamma Release Tests/methods
    • Latent Tuberculosis/blood
    • Mycobacterium tuberculosis/immunology
    • Sensitivity and Specificity
    • T-Lymphocytes/immunology
    • Tuberculin Test
    • Tuberculosis, Pulmonary/blood

    Cite this

    Whitworth, Hilary S. ; Scott, Melanie ; Connell, David W ; Dongés, Bianca ; Lalvani, Ajit. / IGRAs--the gateway to T cell based TB diagnosis. In: Methods (San Diego, Calif.). 2013 ; Vol. 61, No. 1. pp. 52-62.
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    abstract = "Development of Interferon-Gamma Release Assays (IGRAs) and implementation of their use in clinical practice almost 10 years ago has revolutionised diagnosis of latent tuberculosis (TB) infection (LTBI). The commercially available IGRAs, TSPOT.TB (Oxford Immunotech, Oxford, UK) and QuantiFERON Gold In-Tube (Cellestis, Victoria, Australia), allow detection of TB infection with greater specificity and sensitivity than the tuberculin skin test (TST) and are now recommended for diagnosis of LTBI. The TSPOT.TB assay is a simplified enzyme-linked immunospot assay (ELISpot) that enumerates TB-specific T lymphocytes (T cells) secreting interferon-gamma (IFNγ). In comparison, the QuantiFERON Gold In-Tube assay constitutes an enzyme-linked immunosorbent assay (ELISA) to quantify IFNγ released into blood plasma after incubation of whole blood with TB antigens. Release of IFNγ, as a result of antigen stimulation of TB-specific T cells within blood, is indicative of TB infection. Although IGRAs have significant advantages over the TST in diagnosis of latent TB, they have significant limitations. Discovery of new antigens and advances in methodology for measuring cellular immunity have recently paved the way for novel tests that overcome these limitations. By establishing for the first time technological platforms for T cell based diagnosis in diagnostic service laboratories, IGRAs provide a bridgehead to clinical application of T cell based diagnosis in routine practice.",
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    Whitworth, HS, Scott, M, Connell, DW, Dongés, B & Lalvani, A 2013, 'IGRAs--the gateway to T cell based TB diagnosis', Methods (San Diego, Calif.), vol. 61, no. 1, pp. 52-62. https://doi.org/10.1016/j.ymeth.2012.12.012

    IGRAs--the gateway to T cell based TB diagnosis. / Whitworth, Hilary S.; Scott, Melanie; Connell, David W; Dongés, Bianca; Lalvani, Ajit (Lead / Corresponding author).

    In: Methods (San Diego, Calif.), Vol. 61, No. 1, 15.05.2013, p. 52-62.

    Research output: Contribution to journalReview article

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    T1 - IGRAs--the gateway to T cell based TB diagnosis

    AU - Whitworth, Hilary S.

    AU - Scott, Melanie

    AU - Connell, David W

    AU - Dongés, Bianca

    AU - Lalvani, Ajit

    N1 - Copyright © 2013 Elsevier Inc. All rights reserved.

    PY - 2013/5/15

    Y1 - 2013/5/15

    N2 - Development of Interferon-Gamma Release Assays (IGRAs) and implementation of their use in clinical practice almost 10 years ago has revolutionised diagnosis of latent tuberculosis (TB) infection (LTBI). The commercially available IGRAs, TSPOT.TB (Oxford Immunotech, Oxford, UK) and QuantiFERON Gold In-Tube (Cellestis, Victoria, Australia), allow detection of TB infection with greater specificity and sensitivity than the tuberculin skin test (TST) and are now recommended for diagnosis of LTBI. The TSPOT.TB assay is a simplified enzyme-linked immunospot assay (ELISpot) that enumerates TB-specific T lymphocytes (T cells) secreting interferon-gamma (IFNγ). In comparison, the QuantiFERON Gold In-Tube assay constitutes an enzyme-linked immunosorbent assay (ELISA) to quantify IFNγ released into blood plasma after incubation of whole blood with TB antigens. Release of IFNγ, as a result of antigen stimulation of TB-specific T cells within blood, is indicative of TB infection. Although IGRAs have significant advantages over the TST in diagnosis of latent TB, they have significant limitations. Discovery of new antigens and advances in methodology for measuring cellular immunity have recently paved the way for novel tests that overcome these limitations. By establishing for the first time technological platforms for T cell based diagnosis in diagnostic service laboratories, IGRAs provide a bridgehead to clinical application of T cell based diagnosis in routine practice.

    AB - Development of Interferon-Gamma Release Assays (IGRAs) and implementation of their use in clinical practice almost 10 years ago has revolutionised diagnosis of latent tuberculosis (TB) infection (LTBI). The commercially available IGRAs, TSPOT.TB (Oxford Immunotech, Oxford, UK) and QuantiFERON Gold In-Tube (Cellestis, Victoria, Australia), allow detection of TB infection with greater specificity and sensitivity than the tuberculin skin test (TST) and are now recommended for diagnosis of LTBI. The TSPOT.TB assay is a simplified enzyme-linked immunospot assay (ELISpot) that enumerates TB-specific T lymphocytes (T cells) secreting interferon-gamma (IFNγ). In comparison, the QuantiFERON Gold In-Tube assay constitutes an enzyme-linked immunosorbent assay (ELISA) to quantify IFNγ released into blood plasma after incubation of whole blood with TB antigens. Release of IFNγ, as a result of antigen stimulation of TB-specific T cells within blood, is indicative of TB infection. Although IGRAs have significant advantages over the TST in diagnosis of latent TB, they have significant limitations. Discovery of new antigens and advances in methodology for measuring cellular immunity have recently paved the way for novel tests that overcome these limitations. By establishing for the first time technological platforms for T cell based diagnosis in diagnostic service laboratories, IGRAs provide a bridgehead to clinical application of T cell based diagnosis in routine practice.

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    KW - Enzyme-Linked Immunosorbent Assay

    KW - Enzyme-Linked Immunospot Assay

    KW - Humans

    KW - Interferon-gamma/blood

    KW - Interferon-gamma Release Tests/methods

    KW - Latent Tuberculosis/blood

    KW - Mycobacterium tuberculosis/immunology

    KW - Sensitivity and Specificity

    KW - T-Lymphocytes/immunology

    KW - Tuberculin Test

    KW - Tuberculosis, Pulmonary/blood

    U2 - 10.1016/j.ymeth.2012.12.012

    DO - 10.1016/j.ymeth.2012.12.012

    M3 - Review article

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    VL - 61

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    EP - 62

    JO - Methods (San Diego, Calif.)

    JF - Methods (San Diego, Calif.)

    SN - 1046-2023

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