Mycobacteria-Specific Mono- and Polyfunctional CD4+ T Cell Profiles in Children With Latent and Active Tuberculosis: A Prospective Proof-of-Concept Study

Autor: Marc Tebruegge, Nicole Ritz, Susan Donath, Binita Dutta, Benjamin Forbes, Vanessa Clifford, Christel Zufferey, Robert De Rose, Roy M. Robins-Browne, Willem Hanekom, Stephen M. Graham, Tom Connell, Nigel Curtis
Jazyk: angličtina
Rok vydání: 2019
Předmět:
CD4-Positive T-Lymphocytes
0301 basic medicine
lcsh:Immunologic diseases. Allergy
Tuberculosis
diagnosis
T cell
Immunology
Tuberculin
T-Cell Antigen Receptor Specificity
Lymphocyte Activation
Proof of Concept Study
Asymptomatic
Immunophenotyping
Diagnosis
Differential
03 medical and health sciences
0302 clinical medicine
Immune system
Bacterial Proteins
Antigen
Latent Tuberculosis
Humans
Immunology and Allergy
Medicine
Prospective Studies
immunoassay
Cells
Cultured
Original Research
Antigens
Bacterial
child
functional profile
Latent tuberculosis
business.industry
Flow Cytometry
medicine.disease
bacterial infections and mycoses
3. Good health
030104 developmental biology
medicine.anatomical_structure
tuberculosis
Disease Progression
Cytokines
medicine.symptom
business
lcsh:RC581-607
Biomarkers
030215 immunology
Zdroj: Frontiers in Immunology, Vol 10 (2019)
Frontiers in Immunology
ISSN: 1664-3224
Popis: Background: Current immune-based TB tests, including the tuberculin skin test (TST) and interferon-gamma release assays (IGRA), have significant limitations, including the inability to distinguish between latent TB infection (LTBI) and active TB. Few biomarkers with the potential to discriminate between these two infection states have been identified. Objective: To determine whether functional profiling of mycobacteria-specific T cells can distinguish between TB-infected and -uninfected children, and simultaneously discriminate between LTBI and active TB. Methods: One hundred and forty-nine children with suspected active TB or risk factors for LTBI were recruited at the Royal Children's Hospital Melbourne. Whole-blood stimulation assays, using ESAT-6, CFP-10, PPD, and heat-killed M. tuberculosis as stimulants, were done, followed by intracellular cytokine staining and flow cytometric analysis. Results: Eighty-two participants in the well-defined diagnostic categories ‘uninfected individuals’ (asymptomatic, TST 0 mm / IGRA-; n = 61), LTBI (asymptomatic, TST ≥10 mm / IGRA+, normal chest radiograph; n = 15), or active TB [microbiologically-confirmed (n = 3) or fulfilling stringent criteria (n = 3)] were included in the final analysis. The proportions of mycobacteria-specific single-positive TNF-α+ and double-positive IFN-γ+/TNF-α+ CD4+ T cells were significantly higher in participants with active TB than in those with LTBI and uninfected individuals. Additionally, the frequency of IL-17-expressing CD4+ T cells, predominately with single-positive IL-17+ and double-positive IL-2+/IL-17+ phenotypes, was higher in participants with active TB than in the other two groups. Conclusions: The frequencies and functional profiles of mycobacteria-specific CD4+ T cells differ significantly both between TB-infected and TB-uninfected children, and between LTBI and active TB. Although confirmation in further studies will be required, these findings indicate that functional profiling of mycobacteria-specific CD4+ T cells could potentially be exploited for novel immune-based TB assays that enable the distinction between infection states based on a blood sample alone.
Databáze: OpenAIRE
Externí odkaz: