Detection of proliferative responses to ESAT-6 and CFP-10 by FASCIA assay for diagnosis of Mycobacterium tuberculosis infection

Borgström, Erik; Andersen, Peter; Andersson, Lena; Julander, Inger; Källenius, Gunilla; Maeurer, Markus; Norrby, Maria; Rosenkrands, Ida; Tecleab, Teghesti; Bruchfeld, Judith; Gaines, Hans

doi:10.1016/j.jim.2011.05.008

Cited by 17 publications

(12 citation statements)

References 34 publications

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“…Importantly, IFN-g release does not distinguish between active infection and cleared infection because antigen-specifi c memory T cells induced by prior exposure to MTB may persist. 34 These factors collectively provide evidence that IGRA performs poorly as a biomarker of infection clearance following IPT.…”

Section: Quantitative Qft-git Resultsmentioning

confidence: 96%

Effect of Isoniazid Therapy for Latent TB Infection on QuantiFERON-TB Gold In-Tube Responses in Adults With Positive Tuberculin Skin Test Results in a High TB Incidence Area

Johnson

Geldenhuys

Thiel

et al. 2014

Chest

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Section: Quantitative Qft-git Resultsmentioning

confidence: 96%

Effect of Isoniazid Therapy for Latent TB Infection on QuantiFERON-TB Gold In-Tube Responses in Adults With Positive Tuberculin Skin Test Results in a High TB Incidence Area

Johnson

Geldenhuys

Thiel

et al. 2014

Chest

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“…This study was performed on samples used by us in a previous study [31]. Consecutive patients referred to the TB centre at the Clinic of Infectious Diseases at Karolinska University Hospital, Stockholm, Sweden, were recruited to the study between 2006-11-07 and 2008-03-12 after verbal and written informed consent.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2012

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BackgroundThere 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 FindingsConsecutive 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.ConclusionsIP-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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“…Lymphoblasts induced by antigen stimulation were distinguished from resting lymphocytes based on size and granularity [20]. Gating strategy and a representative example are shown in Supplementary Figure 2 …”

Section: Antigen-induced Lymphoblastsmentioning

confidence: 99%

“…Among responders, cytokine profiles were compared using SPICE software, representing relative frequencies of cells producing all 7 combinations of the three examined cytokines [20]. Responders were defined based on total frequency of cytokine-producing cells (IFN-γ and/or TNF-α and/or IL-2).…”

Section: Analysis Of Cytokine Profilementioning

confidence: 99%

Immunological Signatures Identifying Different Stages of Latent Mycobacterium tuberculosis Infection and Discriminating Latent from Active Tuberculosis in Humans

Veronique¹

2015

J Clin Cell Immunol

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Objectives: One third of the world population is considered latently infected with Mycobacterium tuberculosis (LTBI) and sterilizing this reservoir of bacteria that may reactivate is required for tuberculosis (TB) elimination. The group of individuals with LTBI is heterogeneous with some of them being more at risk to develop TB disease than others. Improved diagnosis of subjects with LTBI is needed, allowing to differentiate subjects with LTBI from those with active TB, and to select among LTBI subjects those who are more at risk to develop active TB. We have characterized at the cellular level both the quantitative and qualitative T cell responses to different mycobacterial antigens in selected populations of infected subjects in order to identify new biomarkers that could help to identify M. tuberculosis-infected subjects and to stratify them in risk groups for reactivation of the infection.Methods: lymphoblast frequencies and cytokine production (IFN-γ, TNF-α, IL-2) among CD4 + and CD8 + T cells were analyzed by flow cytometry after in vitro stimulation with the latency antigen heparin-binding haemagglutinin (HBHA) or early-secreted antigen Target-6 (ESAT-6) of peripheral blood mononuclear cells from clinically well characterized M. tuberculosis-infected humans (28 LTBI, 22 TB disease,12 controls). The LTBI group defined according to the Center for Disease Control guidelines was subdivided into QuantiFERON-TB Gold in-Tube (QFT) positive and negative subgroups.Results: similar to TB patients, QFT + LTBI subjects had higher proportions of HBHA-induced TNF-α single+ CD4 + lymphocytes than QFT -LTBI subjects (p<0.05). Compared to LTBI subjects, TB patients had higher frequencies of ESAT-6-induced CD8 + lymphoblasts (p<0.001), higher proportions of ESAT-6-induced IFN-γ + TNF-α + CD4 + T lymphocytes (p<0.05), and lower proportions of HBHA-induced IFN-γ + TNF-α + IL-2 + (p<0.05) CD4 + T lymphocytes.Conclusions: these data provide new biomarkers to discriminate active TB from LTBI, and more interestingly, help to identify LTBI subjects with increased likelihood to develop TB disease.

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Detection of proliferative responses to ESAT-6 and CFP-10 by FASCIA assay for diagnosis of Mycobacterium tuberculosis infection

Cited by 17 publications

References 34 publications

Effect of Isoniazid Therapy for Latent TB Infection on QuantiFERON-TB Gold In-Tube Responses in Adults With Positive Tuberculin Skin Test Results in a High TB Incidence Area

Effect of Isoniazid Therapy for Latent TB Infection on QuantiFERON-TB Gold In-Tube Responses in Adults With Positive Tuberculin Skin Test Results in a High TB Incidence Area

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

Immunological Signatures Identifying Different Stages of Latent Mycobacterium tuberculosis Infection and Discriminating Latent from Active Tuberculosis in Humans

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