Identification of plasma biomarkers for discrimination between tuberculosis infection/disease and pulmonary non tuberculosis disease

Nadia Rosalia Caccamo, Francesco Dieli, Guido Sireci, Paola Di Carlo, Marco Pio La Manna, Paolo Li Donni, Valentina Orlando, Antonio Cascio, Nadia Caccamo, Marco Pio La Manna, Valentina Orlando, Francesco Dieli, Guido Sireci

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Abstract

We used the Luminex Bead Array Multiplex Immunoassay to measure cytokines, chemokines and growth factors responses to the same antigens used for RD1-based Interferon ã Release Assay (IGRA) test. Seventy-nine individuals, 27 active TB, 32 latent infection subsets, 20 individuals derivative purified protein (PPD) negative (subjects that do not have any indurative cutaneous reaction after 72 hrs of intradermal injection of PPD) and with other pulmonary disease were retrospectively studied. Forty-eight analytes were evaluated by Luminex Assay in plasma obtained from whole blood stimulated cells. The diagnostic accuracies of the markers detected were evaluated by ROC curve analysis and by the combination of multiple biomarkers to improve the potential to discriminate between infection/disease and non infection. Among 48 cytokines, 13 analytes, namely IL-3, IL-12-p40, LIF, IFNα2, IL-2ra, IL-13, b-NGF, SCF, TNF-β, TRAIL, IL-2, IFN-γ, IP-10, and MIG, were significantly higher in the active TB and LTBI groups, compared to NON-TB patients, while MIF was significantly lower in active TB patients compared to NON-TB and LTBI groups. The diagnostic accuracies of the markers detected in the culture supernatants evaluated by ROC curve analysis revealed that 11 analytes (IL2, IP10, IFN-γ, IL13, MIG, SCF, b-NGF, IL12-p40, TRAIL, IL2 Ra, LIF) discriminated between NON-TB and LTBI groups, with AUC for all analytes ≥0.73, while 14 analytes (IL2, IP10, IFN-γ, MIG, SCF, b-NGF, IL12-p40, TRAIL, IL2Ra, MIF, TNF-β, IL3, IFN-α2, LIF) discriminated between NON-TB and active TB groups, with AUC ≥0.78, that is a moderate, value in terms of accuracy of a diagnostic test. Finally, the combinations of seven biomarkers resulted in the accurate prediction of 88.89% of active TB patients, 82.35% of subjects with latent infection and 90% of non-TB patients, respectively. Taken together, our data suggest that combinations of whole blood Mycobacterium tuberculosis (Mtb) antigen dependent cytokines production could be useful as biomarkers to determine tuberculosis disease states when compared to non TB cohort.
Lingua originaleEnglish
pagine (da-a)-
Numero di pagine20
RivistaPLoS One
Volume13
Stato di pubblicazionePublished - 2018

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Biomarkers
Pulmonary Tuberculosis
tuberculosis
ROC Curve
Interleukin-2
biomarkers
Tuberculosis
Nerve Growth Factor
Interleukin-12
lymphotoxin
lungs
Plasmas
Lymphotoxin-alpha
cytokines
Interleukin-13
Tuberculin
Cytokines
Infection
infection
Area Under Curve

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cita questo

@article{7af1024be8be4350980f63e0e0368bf9,
title = "Identification of plasma biomarkers for discrimination between tuberculosis infection/disease and pulmonary non tuberculosis disease",
abstract = "We used the Luminex Bead Array Multiplex Immunoassay to measure cytokines, chemokines and growth factors responses to the same antigens used for RD1-based Interferon {\~a} Release Assay (IGRA) test. Seventy-nine individuals, 27 active TB, 32 latent infection subsets, 20 individuals derivative purified protein (PPD) negative (subjects that do not have any indurative cutaneous reaction after 72 hrs of intradermal injection of PPD) and with other pulmonary disease were retrospectively studied. Forty-eight analytes were evaluated by Luminex Assay in plasma obtained from whole blood stimulated cells. The diagnostic accuracies of the markers detected were evaluated by ROC curve analysis and by the combination of multiple biomarkers to improve the potential to discriminate between infection/disease and non infection. Among 48 cytokines, 13 analytes, namely IL-3, IL-12-p40, LIF, IFNα2, IL-2ra, IL-13, b-NGF, SCF, TNF-β, TRAIL, IL-2, IFN-γ, IP-10, and MIG, were significantly higher in the active TB and LTBI groups, compared to NON-TB patients, while MIF was significantly lower in active TB patients compared to NON-TB and LTBI groups. The diagnostic accuracies of the markers detected in the culture supernatants evaluated by ROC curve analysis revealed that 11 analytes (IL2, IP10, IFN-γ, IL13, MIG, SCF, b-NGF, IL12-p40, TRAIL, IL2 Ra, LIF) discriminated between NON-TB and LTBI groups, with AUC for all analytes ≥0.73, while 14 analytes (IL2, IP10, IFN-γ, MIG, SCF, b-NGF, IL12-p40, TRAIL, IL2Ra, MIF, TNF-β, IL3, IFN-α2, LIF) discriminated between NON-TB and active TB groups, with AUC ≥0.78, that is a moderate, value in terms of accuracy of a diagnostic test. Finally, the combinations of seven biomarkers resulted in the accurate prediction of 88.89{\%} of active TB patients, 82.35{\%} of subjects with latent infection and 90{\%} of non-TB patients, respectively. Taken together, our data suggest that combinations of whole blood Mycobacterium tuberculosis (Mtb) antigen dependent cytokines production could be useful as biomarkers to determine tuberculosis disease states when compared to non TB cohort.",
author = "Caccamo, {Nadia Rosalia} and Francesco Dieli and Guido Sireci and {Di Carlo}, Paola and {La Manna}, {Marco Pio} and {Li Donni}, Paolo and Valentina Orlando and Antonio Cascio and Nadia Caccamo and {La Manna}, {Marco Pio} and Valentina Orlando and Francesco Dieli and Guido Sireci",
year = "2018",
language = "English",
volume = "13",
pages = "--",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",

}

TY - JOUR

T1 - Identification of plasma biomarkers for discrimination between tuberculosis infection/disease and pulmonary non tuberculosis disease

AU - Caccamo, Nadia Rosalia

AU - Dieli, Francesco

AU - Sireci, Guido

AU - Di Carlo, Paola

AU - La Manna, Marco Pio

AU - Li Donni, Paolo

AU - Orlando, Valentina

AU - Cascio, Antonio

AU - Caccamo, Nadia

AU - La Manna, Marco Pio

AU - Orlando, Valentina

AU - Dieli, Francesco

AU - Sireci, Guido

PY - 2018

Y1 - 2018

N2 - We used the Luminex Bead Array Multiplex Immunoassay to measure cytokines, chemokines and growth factors responses to the same antigens used for RD1-based Interferon ã Release Assay (IGRA) test. Seventy-nine individuals, 27 active TB, 32 latent infection subsets, 20 individuals derivative purified protein (PPD) negative (subjects that do not have any indurative cutaneous reaction after 72 hrs of intradermal injection of PPD) and with other pulmonary disease were retrospectively studied. Forty-eight analytes were evaluated by Luminex Assay in plasma obtained from whole blood stimulated cells. The diagnostic accuracies of the markers detected were evaluated by ROC curve analysis and by the combination of multiple biomarkers to improve the potential to discriminate between infection/disease and non infection. Among 48 cytokines, 13 analytes, namely IL-3, IL-12-p40, LIF, IFNα2, IL-2ra, IL-13, b-NGF, SCF, TNF-β, TRAIL, IL-2, IFN-γ, IP-10, and MIG, were significantly higher in the active TB and LTBI groups, compared to NON-TB patients, while MIF was significantly lower in active TB patients compared to NON-TB and LTBI groups. The diagnostic accuracies of the markers detected in the culture supernatants evaluated by ROC curve analysis revealed that 11 analytes (IL2, IP10, IFN-γ, IL13, MIG, SCF, b-NGF, IL12-p40, TRAIL, IL2 Ra, LIF) discriminated between NON-TB and LTBI groups, with AUC for all analytes ≥0.73, while 14 analytes (IL2, IP10, IFN-γ, MIG, SCF, b-NGF, IL12-p40, TRAIL, IL2Ra, MIF, TNF-β, IL3, IFN-α2, LIF) discriminated between NON-TB and active TB groups, with AUC ≥0.78, that is a moderate, value in terms of accuracy of a diagnostic test. Finally, the combinations of seven biomarkers resulted in the accurate prediction of 88.89% of active TB patients, 82.35% of subjects with latent infection and 90% of non-TB patients, respectively. Taken together, our data suggest that combinations of whole blood Mycobacterium tuberculosis (Mtb) antigen dependent cytokines production could be useful as biomarkers to determine tuberculosis disease states when compared to non TB cohort.

AB - We used the Luminex Bead Array Multiplex Immunoassay to measure cytokines, chemokines and growth factors responses to the same antigens used for RD1-based Interferon ã Release Assay (IGRA) test. Seventy-nine individuals, 27 active TB, 32 latent infection subsets, 20 individuals derivative purified protein (PPD) negative (subjects that do not have any indurative cutaneous reaction after 72 hrs of intradermal injection of PPD) and with other pulmonary disease were retrospectively studied. Forty-eight analytes were evaluated by Luminex Assay in plasma obtained from whole blood stimulated cells. The diagnostic accuracies of the markers detected were evaluated by ROC curve analysis and by the combination of multiple biomarkers to improve the potential to discriminate between infection/disease and non infection. Among 48 cytokines, 13 analytes, namely IL-3, IL-12-p40, LIF, IFNα2, IL-2ra, IL-13, b-NGF, SCF, TNF-β, TRAIL, IL-2, IFN-γ, IP-10, and MIG, were significantly higher in the active TB and LTBI groups, compared to NON-TB patients, while MIF was significantly lower in active TB patients compared to NON-TB and LTBI groups. The diagnostic accuracies of the markers detected in the culture supernatants evaluated by ROC curve analysis revealed that 11 analytes (IL2, IP10, IFN-γ, IL13, MIG, SCF, b-NGF, IL12-p40, TRAIL, IL2 Ra, LIF) discriminated between NON-TB and LTBI groups, with AUC for all analytes ≥0.73, while 14 analytes (IL2, IP10, IFN-γ, MIG, SCF, b-NGF, IL12-p40, TRAIL, IL2Ra, MIF, TNF-β, IL3, IFN-α2, LIF) discriminated between NON-TB and active TB groups, with AUC ≥0.78, that is a moderate, value in terms of accuracy of a diagnostic test. Finally, the combinations of seven biomarkers resulted in the accurate prediction of 88.89% of active TB patients, 82.35% of subjects with latent infection and 90% of non-TB patients, respectively. Taken together, our data suggest that combinations of whole blood Mycobacterium tuberculosis (Mtb) antigen dependent cytokines production could be useful as biomarkers to determine tuberculosis disease states when compared to non TB cohort.

UR - http://hdl.handle.net/10447/288222

UR - http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0192664&type=printable

M3 - Article

VL - 13

SP - -

JO - PLoS One

JF - PLoS One

SN - 1932-6203

ER -