Immune responses to ESAT-6 and CFP-10 by FASCIA and multiplex technology for diagnosis of M. tuberculosis infection; IP-10 is a promising marker.
BACKGROUND: There is a need for reliable markers to diagnose active and latent tuberculosis (TB). The interferon gamma release assays (IGRAs) are compared to the tuberculin skin test (TST) more specific, but cannot discriminate between recent or remote TB infection. Here the Flow-cytometric Assay fo...
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Public Library of Science (PLoS)
2012-01-01
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Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC3493549?pdf=render |
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author | Emilie Borgström Peter Andersen Fredrik Atterfelt Inger Julander Gunilla Källenius Markus Maeurer Ida Rosenkrands Maria Widfeldt Judith Bruchfeld Hans Gaines |
author_facet | Emilie Borgström Peter Andersen Fredrik Atterfelt Inger Julander Gunilla Källenius Markus Maeurer Ida Rosenkrands Maria Widfeldt Judith Bruchfeld Hans Gaines |
author_sort | Emilie Borgström |
collection | DOAJ |
description | BACKGROUND: There is a need for reliable markers to diagnose active and latent tuberculosis (TB). The interferon gamma release assays (IGRAs) are compared to the tuberculin skin test (TST) more specific, but cannot discriminate between recent or remote TB infection. Here the Flow-cytometric Assay for Specific Cell-mediated Immune-response in Activated whole blood (FASCIA), which quantifies expanded T-lymphoblasts by flow-cytometric analysis after long-term antigen stimulation of whole blood, is combined with cytokine/chemokine analysis in the supernatant by multiplex technology for diagnosis of Mycobacterium tuberculosis (Mtb) infection. METHODS AND FINDINGS: Consecutive patients with suspected TB (n = 85), with microbiologically verified active pulmonary TB (n = 33), extra pulmonary TB (n = 21), clinical TB (n = 11), presumed latent TB infection (LTBI) (n = 23), patients negative for TB (n = 8) and 21 healthy controls were studied. Blood samples were analyzed with FASCIA and multiplex technology to determine and correlate proliferative responses and the value of 14 cytokines for diagnosis of Mtb infection: IFN- γ, IL-2, TNF-α, IP-10, IL-12, IL-6, IL-4, IL-5, IL-13, IL-17, MIP-1β, GM-CSF, IFN-α2 and IL-10. Cytokine levels for IFN-γ, IP-10, MIP-1β, IL-2, TNF-α, IL-6, IL-10, IL-13 and GM-CSF were significantly higher after stimulation with the Mtb specific antigens ESAT-6 and CFP-10 in patients with active TB compared to healthy controls (p<0.05) and correlated with proliferative responses. IP-10 was positive in all patients with verified TB, if using a combination of ESAT-6 and CFP-10 and was the only marker significantly more sensitive in detecting active TB then IFN-γ (p = 0.012). Cytokine responses in patients with active TB were more frequent and detected at higher levels than in patients with LTBI. CONCLUSIONS: IP-10 seems to be an important marker for diagnosis of active and latent TB. Patients with active TB and LTBI responded with similar cytokine profiles against TB antigens but proliferative and cytokine responses were generally higher in patients with active TB. |
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spelling | doaj.art-2570f5192f3c43c88f988d74c84c54cb2022-12-21T23:52:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01711e4343810.1371/journal.pone.0043438Immune responses to ESAT-6 and CFP-10 by FASCIA and multiplex technology for diagnosis of M. tuberculosis infection; IP-10 is a promising marker.Emilie BorgströmPeter AndersenFredrik AtterfeltInger JulanderGunilla KälleniusMarkus MaeurerIda RosenkrandsMaria WidfeldtJudith BruchfeldHans GainesBACKGROUND: There is a need for reliable markers to diagnose active and latent tuberculosis (TB). The interferon gamma release assays (IGRAs) are compared to the tuberculin skin test (TST) more specific, but cannot discriminate between recent or remote TB infection. Here the Flow-cytometric Assay for Specific Cell-mediated Immune-response in Activated whole blood (FASCIA), which quantifies expanded T-lymphoblasts by flow-cytometric analysis after long-term antigen stimulation of whole blood, is combined with cytokine/chemokine analysis in the supernatant by multiplex technology for diagnosis of Mycobacterium tuberculosis (Mtb) infection. METHODS AND FINDINGS: Consecutive patients with suspected TB (n = 85), with microbiologically verified active pulmonary TB (n = 33), extra pulmonary TB (n = 21), clinical TB (n = 11), presumed latent TB infection (LTBI) (n = 23), patients negative for TB (n = 8) and 21 healthy controls were studied. Blood samples were analyzed with FASCIA and multiplex technology to determine and correlate proliferative responses and the value of 14 cytokines for diagnosis of Mtb infection: IFN- γ, IL-2, TNF-α, IP-10, IL-12, IL-6, IL-4, IL-5, IL-13, IL-17, MIP-1β, GM-CSF, IFN-α2 and IL-10. Cytokine levels for IFN-γ, IP-10, MIP-1β, IL-2, TNF-α, IL-6, IL-10, IL-13 and GM-CSF were significantly higher after stimulation with the Mtb specific antigens ESAT-6 and CFP-10 in patients with active TB compared to healthy controls (p<0.05) and correlated with proliferative responses. IP-10 was positive in all patients with verified TB, if using a combination of ESAT-6 and CFP-10 and was the only marker significantly more sensitive in detecting active TB then IFN-γ (p = 0.012). Cytokine responses in patients with active TB were more frequent and detected at higher levels than in patients with LTBI. CONCLUSIONS: IP-10 seems to be an important marker for diagnosis of active and latent TB. Patients with active TB and LTBI responded with similar cytokine profiles against TB antigens but proliferative and cytokine responses were generally higher in patients with active TB.http://europepmc.org/articles/PMC3493549?pdf=render |
spellingShingle | Emilie Borgström Peter Andersen Fredrik Atterfelt Inger Julander Gunilla Källenius Markus Maeurer Ida Rosenkrands Maria Widfeldt Judith Bruchfeld Hans Gaines Immune responses to ESAT-6 and CFP-10 by FASCIA and multiplex technology for diagnosis of M. tuberculosis infection; IP-10 is a promising marker. PLoS ONE |
title | Immune responses to ESAT-6 and CFP-10 by FASCIA and multiplex technology for diagnosis of M. tuberculosis infection; IP-10 is a promising marker. |
title_full | Immune responses to ESAT-6 and CFP-10 by FASCIA and multiplex technology for diagnosis of M. tuberculosis infection; IP-10 is a promising marker. |
title_fullStr | Immune responses to ESAT-6 and CFP-10 by FASCIA and multiplex technology for diagnosis of M. tuberculosis infection; IP-10 is a promising marker. |
title_full_unstemmed | Immune responses to ESAT-6 and CFP-10 by FASCIA and multiplex technology for diagnosis of M. tuberculosis infection; IP-10 is a promising marker. |
title_short | Immune responses to ESAT-6 and CFP-10 by FASCIA and multiplex technology for diagnosis of M. tuberculosis infection; IP-10 is a promising marker. |
title_sort | immune responses to esat 6 and cfp 10 by fascia and multiplex technology for diagnosis of m tuberculosis infection ip 10 is a promising marker |
url | http://europepmc.org/articles/PMC3493549?pdf=render |
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