ArticlePloS one2011
Whole-blood flow-cytometric analysis of antigen-specific CD4 T-cell cytokine profiles distinguishes active tuberculosis from non-active states.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 114 citations in OpenAlex.
- Diagnostic accuracy of IL-2 for the diagnosis of latent tuberculosis: a systematic review and meta-analysis.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2014Pooled it
- Transcriptional Profiling of Human Peripheral Blood Mononuclear Cells Identifies Diagnostic Biomarkers That Distinguish Active and Latent Tuberculosis.Frontiers in immunology · 2019Trial
- Trial
- Tuberculosis prevention: current strategies and future directions.Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases · 2024Review
- Diagnosis and biomarkers for ocular tuberculosis: From the present into the future.Theranostics · 2023Review
- Article
- A virtual host model of Mycobacterium tuberculosis infection identifies early immune events as predictive of infection outcomes.Journal of theoretical biology · 2022Article
- A Small Protein but with Diverse Roles: A Review of EsxA in Mycobacterium-Host Interaction.Cells · 2021Review
- High levels of SARS-CoV-2-specific T cells with restricted functionality in severe courses of COVID-19.JCI insight · 2020Article
- The diagnostic accuracy of Th1 (IFN-γ, TNF-α, and IL-2) and Th2 (IL-4, IL-6 and IL-10) cytokines response in AFB microscopy smear negative PTB- HIV co-infected patients.Scientific reports · 2019Article
- Immune Biomarkers for Diagnosis and Treatment Monitoring of Tuberculosis: Current Developments and Future Prospects.Frontiers in microbiology · 2019Review
- VZV-specific T-cell levels in patients with rheumatic diseases are reduced and differentially influenced by antirheumatic drugs.Arthritis research & therapy · 2018Article
- Active Tuberculosis Is Characterized by Highly Differentiated Effector Memory Th1 Cells.Frontiers in immunology · 2018Article
- Novel M. tuberculosis specific IL-2 ELISpot assay discriminates adult patients with active or latent tuberculosis.PloS one · 2018Article
- IFNγ-producing CD4Clinical and translational medicine · 2017Article
- Review
- Mixed Th1 and Th2 Mycobacterium tuberculosis-specific CD4 T cell responses in patients with active pulmonary tuberculosis from Tanzania.PLoS neglected tropical diseases · 2017Article
- FISH-Flow, a protocol for the concurrent detection of mRNA and protein in single cells using fluorescence in situ hybridization and flow cytometry.Nature protocols · 2017Article
- Flow Cytometric Immune Profiling in Infliximab-Associated Tuberculosis.Clinical medicine insights. Case reports · 2017Article
- Computational and Empirical Studies Predict Mycobacterium tuberculosis-Specific T Cells as a Biomarker for Infection Outcome.PLoS computational biology · 2016Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T-cell based IFN-γ release assays do not permit distinction of active tuberculosis (TB) from successfully treated disease or latent M. tuberculosis infection. We postulated that IFN-γ and IL-2 cytokine profiles of antigen-specific T cells measured by flow-cytometry ex vivo might correlate with TB disease activity in vivo. Tuberculin (PPD), ESAT-6 and CFP-10 were used as stimuli to determine antigen-specific cytokine profiles in CD4 T cells from 24 patients with active TB and 28 patients with successfully treated TB using flow-cytometry. Moreover, 25 individuals with immunity consistent with latent M. tuberculosis infection and BCG-vaccination, respectively, were recruited. Although the frequency of cytokine secreting PPD reactive CD4 T cells was higher in patients with active TB compared to patients with treated TB (median 0.81% vs. 0.39% of CD4 T cells, p = 0.02), the overlap in frequencies precluded distinction between the groups on an individual basis. When assessing cytokine profiles, PPD specific CD4 T cells secreting both IFN-γ and IL-2 predominated in treated TB, latent infection and BCG-vaccination, whilst in active TB the cytokine profile was shifted towards cells secreting IFN-γ only (p<0.0001). Cytokine profiles of ESAT-6 or CFP-10 reactive CD4 T cells did not differ between the groups. Receiver operator characteristics (ROC) analysis revealed that frequencies of PPD specific IFN-γ/IL-2 dual-positive T cells below 56% were an accurate marker for active TB (specificity 100%, sensitivity 70%) enabling effective discrimination from non-active states. In conclusion, a frequency lower than 56% IFN-γ/IL-2 dual positive PPD-specific circulating CD4 T-cells is strongly indicative of active TB.
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