Immunological Biomarkers for Tuberculosis: Potential for a Combinatorial Approach

Pine, Richard; Bushkin, Yuri; Gennaro, Maria Laura

doi:10.1007/978-1-4614-4966-9_10

Cited by 3 publications

(2 citation statements)

References 158 publications

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“…Alternatively, either antibody- or T cell-mediated immune responses elicited in the host are probed. The functional states of effector and memory T cell subsets are often defined by the pattern of expression of cytokines interleukin 2 (IL-2), interferon γ (IFNγ), and tumor necrosis factor α (TNFα) and their phenotypic state is defined by their surface markers such as CD4 and CD8 (1, 2). It has been proposed that the medically significant goal of distinguishing between different stages of some asymptomatic infections, for example, between a stable latent Mycobacterium tuberculosis ( M. tb ) infection and infection that has begun progression to active disease, will require comprehensive characterization of multiple surface markers and secreted cytokines in single T cells responding to antigens (Ag) (1–3).…”

Section: Introductionmentioning

confidence: 99%

Profiling T Cell Activation Using Single-Molecule Fluorescence In Situ Hybridization and Flow Cytometry

Bushkin

Radford

Pine

et al. 2015

The Journal of Immunology

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Flow cytometric characterization of antigen-specific T cells typically relies on detection of protein analytes. Shifting the analysis to detection of RNA would provide several significant advantages, which we illustrate by developing a new host immunity-based platform for detection of infections. Cytokine mRNAs synthesized in response to ex vivo stimulation with pathogen-specific antigens are detected in T cells with single molecule-fluorescence in situ hybridization followed by flow cytometry. Background from pre-existing in vivo analytes is lower for RNAs than for proteins, allowing greater sensitivity for detection of low frequency cells. Moreover, mRNA analysis reveals kinetic differences in cytokine expression that are not apparent at the protein level but provide novel insights into gene expression programs expected to define different T cell subsets. The utility of probing immunological memory of infections is demonstrated by detecting T cells that recognize mycobacterial and viral antigens in donors exposed to the respective pathogens.

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Section: Introductionmentioning

confidence: 99%

Profiling T Cell Activation Using Single-Molecule Fluorescence In Situ Hybridization and Flow Cytometry

Bushkin

Radford

Pine

et al. 2015

The Journal of Immunology

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“…1) and was previously introduced to study Mycobacterium tuberculosis-specific T cells. [12][13][14] FISH-Flow will likely find many uses in immunological research and development of diagnostic technologies for infectious disease.…”

Section: Introductionmentioning

confidence: 99%

Flow Cytometric Characterization of Antigen-Specific T Cells Based on RNA and Its Advantages in Detecting Infections and Immunological Disorders

et al. 2016

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Fluorescence in situ hybridization coupled with flow cytometry (FISH-Flow) is a highly quantitative, high-throughput platform allowing precise quantification of total mRNA transcripts in single cells. In undiagnosed infections posing a significant health burden worldwide, such as latent tuberculosis or asymptomatic recurrent malaria, an important challenge is to develop accurate diagnostic tools. Antigen-specific T cells create a persistent memory to pathogens, making them useful for diagnosis of infection. Stimulation of memory response initiates T-cell transitions between functional states. Numerous studies have shown that changes in protein levels lag real-time T-cell transitions. However, analysis at the single-cell transcriptional level can determine the differences. FISH-Flow is a powerful tool with which to study the functional states of T-cell subsets and to identify the gene expression profiles of antigen-specific T cells during disease progression. Advances in instrumentation, fluorophores, and FISH methodologies will broaden and deepen the use of FISH-Flow, changing the immunological field by allowing determination of functional immune signatures at the mRNA level and the development of new diagnostic tools.

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Bacterial pili, with emphasis onMycobacterium tuberculosiscurli pili: potential biomarkers for point-of care tests and therapeutics

Naidoo

Pillay

2016

Biomarkers

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Immunological Biomarkers for Tuberculosis: Potential for a Combinatorial Approach

Cited by 3 publications

References 158 publications

Profiling T Cell Activation Using Single-Molecule Fluorescence In Situ Hybridization and Flow Cytometry

Profiling T Cell Activation Using Single-Molecule Fluorescence In Situ Hybridization and Flow Cytometry

Flow Cytometric Characterization of Antigen-Specific T Cells Based on RNA and Its Advantages in Detecting Infections and Immunological Disorders

Bacterial pili, with emphasis onMycobacterium tuberculosiscurli pili: potential biomarkers for point-of care tests and therapeutics

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