Detection of interleukin-2 in addition to interferon-γ discriminates active tuberculosis patients, latently infected individuals, and controls

Biselli, Roberto; Mariotti, Sabrina; Sargentini, Valeria; Sauzullo, Ilaria; Lastilla, M; Mengoni, Fabio; Vanini, Valentina; Girardi, Enrico; Goletti, Delia; Amelio, R; Nisini, Roberto

doi:10.1111/j.1469-0691.2009.03104.x

Cited by 95 publications

(74 citation statements)

References 12 publications

(15 reference statements)

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“…Measurement of additional cytokines secreted by peripheral In one study, levels of IL-2 measured after prolonged incubation (72 h) of PBMCs with the antigens used in IGRAs were higher in LTBI than in active disease (11). The diagnostic potential of IP-10 (125) also has been evaluated, with mixed results (54,149,167).…”

Section: Cellular Immune Responses and Infection Statementioning

confidence: 99%

Immunodiagnosis of Tuberculosis: a Dynamic View of Biomarker Discovery

Kunnath-Velayudhan¹,

Gennaro²

2011

Clin Microbiol Rev

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SUMMARY Infection with Mycobacterium tuberculosis causes a variety of clinical conditions ranging from life-long asymptomatic infection to overt disease with increasingly severe tissue damage and a heavy bacillary burden. Immune biomarkers should follow the evolution of infection and disease because the host immune response is at the core of protection against disease and tissue damage in M. tuberculosis infection. Moreover, levels of immune markers are often affected by the antigen load. We review how the clinical spectrum of M. tuberculosis infection correlates with the evolution of granulomatous lesions and how granuloma structural changes are reflected in the peripheral circulation. We also discuss how antigen-specific, peripheral immune responses change during infection and how these changes are associated with the physiology of the tubercle bacillus. We propose that a dynamic approach to immune biomarker research should overcome the challenges of identifying those asymptomatic and symptomatic stages of infection that require antituberculosis treatment. Implementation of such a view requires longitudinal studies and a systems immunology approach leading to multianalyte assays.

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Section: Cellular Immune Responses and Infection Statementioning

confidence: 99%

Immunodiagnosis of Tuberculosis: a Dynamic View of Biomarker Discovery

Kunnath-Velayudhan¹,

Gennaro²

2011

Clin Microbiol Rev

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“…52,53 The main limitation of this study is the inclusion of a limited number of patients with active TB, a limitation shared by many other studies in this area. 23,26,27,29,34,38 detection of statistical differences between the diagnostic groups. An important strength of this study is the use of unambiguous diagnostic groups in the analyses.…”

Section: Receiver Operating Characteristic Analysesmentioning

confidence: 99%

Mycobacteria-Specific Cytokine Responses Detect Tuberculosis Infection and Distinguish Latent from Active Tuberculosis

Tebruegge

Dutta

Donath

et al. 2015

Am J Respir Crit Care Med

101

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“…While some reports support this view in human M. tuberculosis infection (i.e., that T cells from people with advanced or active TB only, but not latent TB, secrete IL-2 after specific stimulation [23,24]), other reports suggest that the reverse may be true. Sester et al (25), using flow cytometry, and Casey et al (26), using a dualpurpose IFN-␥/IL-2 ELISPOT assay (both reports from the same group), showed increases in T cells producing both IFN-␥ and IL-2, or IL-2 only in protected (BCG vaccinated, treated, or latently infected) individuals and not in people with active TB who had more T cells producing IFN-␥.…”

Section: Discussionmentioning

confidence: 79%

Use of Antigen-Specific Interleukin-2 To Differentiate between Cattle Vaccinated with Mycobacterium bovis BCG and Cattle Infected with M. bovis

Rhodes

McKinna

Steinbach

et al. 2013

Clin. Vaccine Immunol.

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bWe describe here the application of a novel bovine interleukin-2 (IL-2) enzyme-linked immunosorbent assay (ELISA) for the measurement of antigen-specific IL-2 in cattle naturally infected with Mycobacterium bovis and in cattle vaccinated with Mycobacterium bovis BCG and then experimentally challenged with pathogenic M. bovis. Supernatants from whole-blood cultures stimulated with mycobacterial antigen (bovine purified protein derivative [PPDB] or the peptide cocktail ESAT6-CFP10) were assessed using a sandwich ELISA consisting of a new recombinant monoclonal fragment capture antibody and a commercially available polyclonal anti-bovine-IL-2. The production of IL-2 was compared to the production of gamma interferon (IFN-␥) in the same antigen-stimulated whole-blood supernatants. The data show that cattle infected with M. bovis produced quantifiable levels of antigen-specific IL-2, while IL-2 levels in cattle vaccinated with M. bovis BCG did not. Furthermore, cattle vaccinated with M. bovis BCG and then challenged with pathogenic M. bovis displayed a more rapid induction of IL-2 but ultimately had lower levels of infection-induced IL-2 than did unvaccinated challenge control cattle. These data suggest that IL-2 responses are not detectable post-BCG vaccination and that these responses may require infection with virulent M. bovis to develop. This may be useful to differentiate infected cattle from uninfected or BCG-vaccinated cattle, although the overall sensitivity is relatively low, particularly in single intradermal comparative cervical tuberculin (SICCT)-negative infected animals. Furthermore, the strength of the IL-2 response may correlate with pathology, which poses interesting questions on the immunobiology of bovine tuberculosis in contrast to human tuberculosis, which is discussed.

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Detection of interleukin-2 in addition to interferon-γ discriminates active tuberculosis patients, latently infected individuals, and controls

Cited by 95 publications

References 12 publications

Immunodiagnosis of Tuberculosis: a Dynamic View of Biomarker Discovery

Immunodiagnosis of Tuberculosis: a Dynamic View of Biomarker Discovery

Mycobacteria-Specific Cytokine Responses Detect Tuberculosis Infection and Distinguish Latent from Active Tuberculosis

Use of Antigen-Specific Interleukin-2 To Differentiate between Cattle Vaccinated with Mycobacterium bovis BCG and Cattle Infected with M. bovis

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