Skip to main content
Top
Published in: Medical Microbiology and Immunology 2/2019

01-04-2019 | Tuberculosis | Original Investigation

Diagnostic performance in active TB of QFT-Plus assay and co-expression of CD25/CD134 in response to new antigens of Mycobacterium tuberculosis

Authors: Ilaria Sauzullo, Fabio Mengoni, Claudia Mascia, Paolo Pavone, Giulia Savelloni, Anna Paola Massetti, Miriam Lichtner, Vincenzo Vullo, Claudio M. Mastroianni

Published in: Medical Microbiology and Immunology | Issue 2/2019

Login to get access

Abstract

The new QuantiFERON-TB Gold Plus employs modified peptides optimized to elicit an IFNγ response from CD8+ cytotoxic T lymphocytes in addition to CD4+ T cells. With a view to improve the difficult identification of TB cases, we assessed the combination of two specific immunological markers comprising IFNγ secretion and T cells co-expression of CD25 and CD134 in response to Mycobacterium tuberculosis-specific antigens. A total of 34 subjects with suspected TB and 10 age-matched HD were prospectively enrolled. Assessing the performance of QFT-Plus in terms of the TB1 and TB2 results, we found that in TB patients, the quantitative IFNγ value in TB2 was similar to that in TB1, and we did not find any differences irrespective of the disease (pulmonary or extra-pulmonary). The flow cytometric CD25/CD134 assay, allowed a more accurate differentiation between M. tuberculosis-infected and uninfected patients, with a better combination of sensitivity and specificity, especially by evaluation of CD4+ T-cell subset. All individuals with negative QFT-Plus results displayed a positive CD25/CD134 response. Overall, a positive correlation was found between T cells co-expressing CD25/CD134 and IFNγ levels in response to both QFT-Plus TB antigen tubes, as well as between the QFT-Plus TB1 and TB2 tubes. We demonstrated that both TB1 and TB2 induce a higher expression of CD25+CD134+ markers on CD4+ T cells among infected TB subjects, compared to the lower degree of CD8+ T cells, mainly induced to TB2 stimulation. We suggest that a combined use of classic QFT-Plus and specific CD25/CD134 response may be a useful means in the diagnostic workup for active TB.
Literature
2.
go back to reference Fry DE (2016) Extra-pulmonary tuberculosis and its surgical treatment. Surg Infect 17:394–401CrossRef Fry DE (2016) Extra-pulmonary tuberculosis and its surgical treatment. Surg Infect 17:394–401CrossRef
3.
go back to reference Ali Chaudhry L, Al-Solaiman S (2013) Multifocal tuberculosis: many faces of an old menace. Int J Mycobacteriol 2:58–69CrossRefPubMed Ali Chaudhry L, Al-Solaiman S (2013) Multifocal tuberculosis: many faces of an old menace. Int J Mycobacteriol 2:58–69CrossRefPubMed
5.
go back to reference Whitworth HS, Scott M, Connell DW, Dongés B, Lalvani A (2013) IGRAs—the gateway to T cell based TB diagnosis. Methods 61:52–62CrossRefPubMed Whitworth HS, Scott M, Connell DW, Dongés B, Lalvani A (2013) IGRAs—the gateway to T cell based TB diagnosis. Methods 61:52–62CrossRefPubMed
6.
go back to reference Andersen P, Munk ME, Pollock JM, Doherty TM (2000) Specific immune-based diagnosis of tuberculosis. Lancet 356:1099–1104CrossRefPubMed Andersen P, Munk ME, Pollock JM, Doherty TM (2000) Specific immune-based diagnosis of tuberculosis. Lancet 356:1099–1104CrossRefPubMed
11.
go back to reference Chen X, Zhou B, Li M, Deng Q, Wu X, Le X et al (2007) CD4 + CD25 + FoxP3 + regulatory T cells suppress Mycobacterium tuberculosis immunity in patients with active disease. Clin Immunol 123:50–59CrossRefPubMed Chen X, Zhou B, Li M, Deng Q, Wu X, Le X et al (2007) CD4 + CD25 + FoxP3 + regulatory T cells suppress Mycobacterium tuberculosis immunity in patients with active disease. Clin Immunol 123:50–59CrossRefPubMed
12.
go back to reference Ferrara G, Losi M, Meacci M, Meccugni B, Piro R, Roversi P et al (2005) Routine hospital use of a new commercial whole blood interferon-gamma assay for the diagnosis of tuberculosis infection. Am J Respir Crit Care Med 172:631–635CrossRefPubMed Ferrara G, Losi M, Meacci M, Meccugni B, Piro R, Roversi P et al (2005) Routine hospital use of a new commercial whole blood interferon-gamma assay for the diagnosis of tuberculosis infection. Am J Respir Crit Care Med 172:631–635CrossRefPubMed
13.
go back to reference Kim K, Perera R, Tan DBA, Fernandez S, Seddiki N, Waring, French MA (2014) Circulating mycobacterial-reactive CD4 + T cells with an immunosuppressive phenotype are higher in active tuberculosis than latent tuberculosis infection. Tuberculosis 94:450–494 Kim K, Perera R, Tan DBA, Fernandez S, Seddiki N, Waring, French MA (2014) Circulating mycobacterial-reactive CD4 + T cells with an immunosuppressive phenotype are higher in active tuberculosis than latent tuberculosis infection. Tuberculosis 94:450–494
14.
go back to reference Serbina NV, Lazarevic V, Flynn JL (2001) CD4 (+) T cells are required for the development of cytotoxic CD8(+) T cells during Mycobacterium tuberculosis infection. J Immunol 167:6991–7000CrossRefPubMed Serbina NV, Lazarevic V, Flynn JL (2001) CD4 (+) T cells are required for the development of cytotoxic CD8(+) T cells during Mycobacterium tuberculosis infection. J Immunol 167:6991–7000CrossRefPubMed
22.
go back to reference Nicol MP, Sola C, February B, Rastogi N, Steyn L, Wilkinson RJ (2005) Distribution of strain families of Mycobacterium tuberculosis causing pulmonary and extrapulmonary disease in hospitalized children in Cape Town, South Africa. J Clin Microbiol 43:5779–5781CrossRefPubMedPubMedCentral Nicol MP, Sola C, February B, Rastogi N, Steyn L, Wilkinson RJ (2005) Distribution of strain families of Mycobacterium tuberculosis causing pulmonary and extrapulmonary disease in hospitalized children in Cape Town, South Africa. J Clin Microbiol 43:5779–5781CrossRefPubMedPubMedCentral
23.
go back to reference Pathan AA, Wilkinson KA, Klenerman P, McShane H, Davidson RN, Pasvol G et al (2001) Direct ex vivo analysis of antigen specific IFN-gamma—secreting CD4 T cells in Mycobacterium tuberculosis-infected individuals: associations with clinical disease state and effect of treatment. J Immunol 167:5217–5225CrossRefPubMed Pathan AA, Wilkinson KA, Klenerman P, McShane H, Davidson RN, Pasvol G et al (2001) Direct ex vivo analysis of antigen specific IFN-gamma—secreting CD4 T cells in Mycobacterium tuberculosis-infected individuals: associations with clinical disease state and effect of treatment. J Immunol 167:5217–5225CrossRefPubMed
24.
go back to reference Jafari C, Thijsen S, Sotgiu G, Goletti D, Dominguez Benitez JA, Losi M et al (2009) Bronchoalveolar lavage enzyme-linked immunospot for a rapid diagnosis of tuberculosis: a Tuberculosis Network European Trials group study. Am J Respir Crit Care Med 180:666–673CrossRefPubMedPubMedCentral Jafari C, Thijsen S, Sotgiu G, Goletti D, Dominguez Benitez JA, Losi M et al (2009) Bronchoalveolar lavage enzyme-linked immunospot for a rapid diagnosis of tuberculosis: a Tuberculosis Network European Trials group study. Am J Respir Crit Care Med 180:666–673CrossRefPubMedPubMedCentral
25.
go back to reference Croft M (2003) Co-stimulatory members of the TNFR family: keys to effective T cell immunity? Nat Rev Immunol 3:609–620CrossRefPubMed Croft M (2003) Co-stimulatory members of the TNFR family: keys to effective T cell immunity? Nat Rev Immunol 3:609–620CrossRefPubMed
26.
go back to reference Lenardo M, Chan KM, Hornung F, McFarland H, Siegel R, Wang J, Zheng L (1999) Mature T lymphocyte apoptosis-immune regulation in a dynamic and unpredictable antigenic environment. Ann Rev Immunol 17:221–253CrossRef Lenardo M, Chan KM, Hornung F, McFarland H, Siegel R, Wang J, Zheng L (1999) Mature T lymphocyte apoptosis-immune regulation in a dynamic and unpredictable antigenic environment. Ann Rev Immunol 17:221–253CrossRef
28.
go back to reference Brookes RH, Pathan AA, McShane H, Hensmann M, Price DA, Hill AV (2003) CD8 + T cell-mediated suppression of intracellular Mycobacterium tuberculosis growth in activated human macrophages. Eur J Immunol 33:3293–3302CrossRefPubMed Brookes RH, Pathan AA, McShane H, Hensmann M, Price DA, Hill AV (2003) CD8 + T cell-mediated suppression of intracellular Mycobacterium tuberculosis growth in activated human macrophages. Eur J Immunol 33:3293–3302CrossRefPubMed
31.
32.
go back to reference Lewinsohn DA, Heinzel AS, Gardner JM, Zhu L, Alderson MR, Lewinsohn DM (2003) Mycobacterium tuberculosis-specific CD8 + T cells preferentially recognize heavily infected cells. Am J Respir Crit Care Med 168:1346–1352CrossRefPubMed Lewinsohn DA, Heinzel AS, Gardner JM, Zhu L, Alderson MR, Lewinsohn DM (2003) Mycobacterium tuberculosis-specific CD8 + T cells preferentially recognize heavily infected cells. Am J Respir Crit Care Med 168:1346–1352CrossRefPubMed
36.
go back to reference Caccamo N, Meraviglia S, La Mendola C, Guggino G, Dieli F, Salerno A (2006) Phenotypical and functional analysis of memory and effector human CD8 T cells specific for mycobacterial antigens. J Immunol 177:1780–1785CrossRefPubMed Caccamo N, Meraviglia S, La Mendola C, Guggino G, Dieli F, Salerno A (2006) Phenotypical and functional analysis of memory and effector human CD8 T cells specific for mycobacterial antigens. J Immunol 177:1780–1785CrossRefPubMed
37.
go back to reference Dieli F, Friscia G, Di Sano C, Ivanyi J, Singh M, Spallek R et al (1999) Sequestration of T lymphocytes to body fluids in tuberculosis: reversal of anergy following chemotherapy. J Infect Dis 180:225–228CrossRefPubMed Dieli F, Friscia G, Di Sano C, Ivanyi J, Singh M, Spallek R et al (1999) Sequestration of T lymphocytes to body fluids in tuberculosis: reversal of anergy following chemotherapy. J Infect Dis 180:225–228CrossRefPubMed
40.
go back to reference Ribeiro-Rodrigues R, Resende Co T, Rojas R, Toossi Z, Dietze R, Boom WH et al (2006) A role for CD4 + CD25 + T cells in regulation of the immune response during human tuberculosis. Clin Exp Immunol 144:25–34CrossRefPubMedPubMedCentral Ribeiro-Rodrigues R, Resende Co T, Rojas R, Toossi Z, Dietze R, Boom WH et al (2006) A role for CD4 + CD25 + T cells in regulation of the immune response during human tuberculosis. Clin Exp Immunol 144:25–34CrossRefPubMedPubMedCentral
Metadata
Title
Diagnostic performance in active TB of QFT-Plus assay and co-expression of CD25/CD134 in response to new antigens of Mycobacterium tuberculosis
Authors
Ilaria Sauzullo
Fabio Mengoni
Claudia Mascia
Paolo Pavone
Giulia Savelloni
Anna Paola Massetti
Miriam Lichtner
Vincenzo Vullo
Claudio M. Mastroianni
Publication date
01-04-2019
Publisher
Springer Berlin Heidelberg
Published in
Medical Microbiology and Immunology / Issue 2/2019
Print ISSN: 0300-8584
Electronic ISSN: 1432-1831
DOI
https://doi.org/10.1007/s00430-018-00576-4

Other articles of this Issue 2/2019

Medical Microbiology and Immunology 2/2019 Go to the issue