scholarly journals Antigen-Specific Cytokine and Chemokine Gene Expression for Diagnosing Latent and Active Tuberculosis

Diagnostics ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 716
Author(s):  
Workneh Korma ◽  
Adane Mihret ◽  
Yunhee Chang ◽  
Azeb Tarekegn ◽  
Metasebiya Tegegn ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pulmonary Tuberculosis ◽  
Sensitivity And Specificity ◽  
Interferon Gamma ◽  
Active Tuberculosis ◽  
Tuberculosis Infection ◽  
Tuberculosis Patients ◽  
Cytokines And Chemokines ◽  
Ifn Γ ◽  
Sensitivity Specificity

Tuberculosis infection exhibits different forms, namely, pulmonary, extrapulmonary, and latent. Here, diagnostic markers based on the gene expression of cytokines and chemokines for differentiating between tuberculosis infection state(s) were identified. Gene expression of seven cytokines (Interferon gamma (IFN-γ), Interferon gamma-induced protein 10 (IP-10), Interleukin-2 receptor (IL-2R), C-X-C Motif Chemokine Ligand 9 (CXCL-9), Interleukin 10 (IL-10), Interleukin 4 (IL-4), and Tumor Necrosis Factor alpha (TNF-α)) in response to tuberculosis antigen was analyzed using real-time polymerase reaction. The sensitivity and specificity of relative quantification (2^-ΔΔCt) of mRNA expression were analyzed by constructing receiver operating characteristic curves and measuring the area under the curve (AUC) values. Combinations of cytokines were analyzed using the R statistical software package. IFN-γ, IP-10, IL2R, and CXCL-9 showed high expression in latent and active tuberculosis patients (p = 0.001), with a decrease in IL10 expression, and no statistical difference in IL-4 levels among all the groups (p = 0.999). IL-10 differentiated pulmonary tuberculosis patients from latent cases with an AUC of 0.731. IL10 combined with CXCL-9 distinguished pulmonary tuberculosis patients from extrapulmonary cases with a sensitivity, specificity, and accuracy of 85.7%, 73.9%, and 81.0%, respectively. IL-10 together with IP-10 and IL-4 differentiated pulmonary tuberculosis from latent cases with a sensitivity and specificity of 77.1% and 88.1%, respectively. Decision tree analysis demonstrated that IFN-γ IL-2R, and IL-4 can diagnose tuberculosis infection with a sensitivity, specificity, and accuracy of 89.7%, 96.1%, and 92.7%, respectively. A combination of gene expression of cytokines and chemokines might serve as an effective marker to differentiate tuberculosis infection state(s).

scholarly journals Increased Numbers of ESAT-6- and Purified Protein Derivative-Specific Gamma Interferon-Producing Cells in Subclinical and Active Tuberculosis Infection

2000 ◽  
Vol 68 (10) ◽  
pp. 6073-6076 ◽  
Author(s):  
Timo Ulrichs ◽  
Peter Anding ◽  
Steven Porcelli ◽  
Stefan H. E. Kaufmann ◽  
Martin E. Munk
Keyword(s):  
Mycobacterium Bovis ◽  
Synthetic Peptides ◽  
Gamma Interferon ◽  
Active Tuberculosis ◽  
Tuberculosis Infection ◽  
Potential Candidate ◽  
Tuberculosis Patients ◽  
Purified Protein Derivative ◽  
Healthy Donors ◽  
Ifn Γ

ABSTRACT Numbers of gamma interferon (IFN-γ)-producing cells reactive to ESAT-6 antigen were increased in recent converters to purified protein derivative positivity and in tuberculosis patients but not in unvaccinated or Mycobacterium bovis BCG-vaccinated healthy donors. ESAT-6-reactive IFN-γ-producing cells in recent converters and tuberculosis patients recognized similar synthetic peptides. Thus, ESAT-6 is a potential candidate for use in detection of early, as well as active, tuberculosis and for control of the disease.

scholarly journals Utility of interferon gamma/tumor necrosis factor alpha FluoroSpot assay in differentiation between active tuberculosis and latent tuberculosis infection: a pilot study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lifan Zhang ◽  
Shijun Wan ◽  
Ziyue Zhou ◽  
Yueqiu Zhang ◽  
Xiaoqing Liu
Keyword(s):  
T Cells ◽  
Pilot Study ◽  
Diagnostic Accuracy ◽  
Latent Tuberculosis Infection ◽  
Latent Tuberculosis ◽  
Active Tuberculosis ◽  
Tuberculosis Infection ◽  
Tnf Α ◽  
Ifn Γ ◽  
Sensitivity Specificity

Abstract Background The differential diagnosis of active tuberculosis (ATB) and latent tuberculosis infection (LTBI) remains challenging in clinical practice. We aimed to evaluate the diagnostic accuracy of the IFN-γ/TNF-α FluoroSpot assay for differentiating ATB from LTBI. Methods We conducted a pilot study of case-control design, using the FluoroSpot assay to simultaneously detect IFN-γ and TNF-α secretion at the single-cell level. The frequencies of antigen-specific single TNF-α-, total TNF-α-, single IFN-γ-, total IFN-γ- and dual IFN-γ/TNF-α-secreting T cells were detected. The optimal cutoffs value of frequencies for differentiating ATB from LTBI were determined according to receiver operating characteristic curve analysis. The sensitivity, specificity, predictive values (PV) and likelihood ratios (LR) of the FluoroSpot assay were calculated. Results Thirty patients diagnosed microbiologically with ATB, 36 healthcare workers with LTBI and 36 healthy controls were enrolled. After stimulated by ESAT-6 or CFP-10 peptides, the median frequencies of single TNF-α-, total TNF-α-, single IFN-γ-, total IFN-γ- and dual IFN-γ/TNF-α-secreting T cells in ATB patients were all significantly higher than those in LTBI and HC groups (P < 0.01). The frequencies of total IFN-γ-secreting T cells detected by FluoroSpot assay correlated significantly with those of T-SPOT.TB (r = 0.910 for ESAT-6, P < 0.001, r = 0.845 for CFP-10, P < 0.001). After stimulated by ESAT-6 peptides, with total TNF-α-secreting T cells frequencies at a cut off value of 21 iSFCs/250,000 PBMCs, the sensitivity, specificity, PLR, NLR, PPV, NPV of IFN-γ/TNF-α FluoroSpot assay in differentiating ATB from LTBI were 96.7% (95%CI, 82.8–99.9%), 94.3% (95%CI, 80.8–99.3%), 16.92 (95%CI, 4.40–65.08), 0.04 (95%CI, 0.01–0.24), 93.6% (95%CI,78.6–99.2%) and 97.1% (95%CI, 84.7–99.9%), respectively. With the frequencies of total TNF-α- and total IFN-γ-secreting T cells stimulated by ESAT-6 peptides combined, the specificity was increased to 97.1%, and the positive likelihood ratio to 31.5. The combination with CFP-10 might not improve the diagnostic accuracy of the ESAT-6 for differentiating ATB from LTBI. Conclusions IFN-γ/TNF-α FluoroSpot assay might have potential to help differentiate ATB from LTBI, but the findings need to be further verified by cross-sectional or prospective cohort studies.

scholarly journals Comparative accuracy of pleural fluid unstimulated interferon-gamma and adenosine deaminase for diagnosing pleural tuberculosis: A systematic review and meta-analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0253525
Author(s):  
Ashutosh Nath Aggarwal ◽  
Ritesh Agarwal ◽  
Sahajal Dhooria ◽  
Kuruswamy Thurai Prasad ◽  
Inderpaul Singh Sehgal ◽  
...  
Keyword(s):  
Systematic Review ◽  
Diagnostic Accuracy ◽  
Adenosine Deaminase ◽  
Pleural Fluid ◽  
Sensitivity And Specificity ◽  
Interferon Gamma ◽  
Meta Analysis ◽  
Paired Data ◽  
Ifn Γ ◽  
Meta Regression

Objective We compared diagnostic accuracy of pleural fluid adenosine deaminase (ADA) and interferon-gamma (IFN-γ) in diagnosing tuberculous pleural effusion (TPE) through systematic review and comparative meta-analysis. Methods We queried PubMed and Embase databases to identify studies providing paired data for sensitivity and specificity of both pleural fluid ADA and IFN-γ for diagnosing TPE. We used hierarchical summary receiver operating characteristic (HSROC) plots and HSROC meta-regression to model individual and comparative diagnostic performance of the two tests. Results We retrieved 376 citations and included 45 datasets from 44 publications (4974 patients) in our review. Summary estimates for sensitivity and specificity for ADA were 0.88 (95% CI 0.85–0.91) and 0.91 (95% CI 0.89–0.92), while for IFN-γ they were 0.91 (95% CI 0.89–0.94) and 0.96 (95% CI 0.94–0.97), respectively. HSROC plots showed consistently greater diagnostic accuracy for IFN-γ over ADA across the entire range of observations. HSROC meta-regression using test-type as covariate yielded a relative diagnostic odds ratio of 2.22 (95% CI 1.68–2.94) in favour of IFN-γ, along with better summary sensitivity and specificity figures. No prespecified subgroup variable significantly influenced the summary diagnostic accuracy estimates. Conclusion Pleural fluid IFN-γ estimation has better diagnostic accuracy than ADA estimation for diagnosis of TPE.

scholarly journals KORELASI KADAR SERUM IFN-γ, EKSPRESI DAN FUNGSI RESEPTOR IFN-γ, DENGAN KEJADIAN TUBERKULOSIS PARU (The Correlation Of Ifn-γ Serum Level, Ifn-γ Receptor Expression And Function, With Pulmonary Tuberculosis)

2013 ◽  
Vol 3 (3) ◽  
Author(s):  
Jahja Teguh Widjaja
Keyword(s):  
Stem Cell ◽  
Serum Level ◽  
Pulmonary Tuberculosis ◽  
Mononuclear Cells ◽  
Receptor Expression ◽  
Cross Sectional ◽  
Tuberculosis Patients ◽  
Ifn Γ ◽  
Cross Sectional Design ◽  
And Function

AbstrakUntuk dapat bekerja dengan efektif menghadapi M. tuberculosis, sistim imunitas seluler memerlukan kadar IFN-γ dan reseptor IFN-γ di sel-sel mononuklear yang bekerja optimal. Tujuan penelitian ini adalah menganalisis korelasi antara kadar serum IFN-, ekspresi dan fungsi reseptor IFN-γ, dengan kejadian penyakit Tuberkulosis Paru. Observasi analitik dengan rancangan potong silang yang membandingkan kadar serum IFN-γ, fungsi dan ekspresi reseptor IFN-γ, pada pasien TB Paru dengan pasangannya yang sehat, serta menganalisis korelasi antara variabel-variabel tersebut dengan kejadian penyakit TB Paru. Penelitian dilakukan pada Juli 2009 sampai September 2010, di RS Immanuel Bandung dan laboratorium Stem Cell & Cancer Institute, Jakarta. Dibandingkan pasangan hidupnya, kadar serum IFN-γ pasien TB tidak berbeda bermakna, ekspresi reseptor IFN-γ pasien TB lebih tinggi (p=0,041), sedangkan fungsi reseptor IFN-γ pasien TB lebih rendah (p=0,011). Analisis korelasi mendapatkan satusatunya variabel yang mempunyai korelasi bermakna dengan kejadian tuberkulosis paru adalah fungsi reseptor IFN-γ yang rendah (p=0,026, OR 5,56). Pada pasien TB Paru ekspresi reseptor IFN-γ lebih tinggi, tetapi fungsi reseptor IFN-γ lebih rendah dari pasangan hidup sehat. Fungsi reseptor IFN-γ yang rendah ini mempunyai korelasi bermakna dengan kejadian tuberkulosis paru.Kata kunci: tuberkulosis, kadar serum IFN-γ, ekspresi dan fungsi reseptor IFN-γ.AbstractIn order to work effectively against M. tuberculosis, the cell mediated immune system needs serum level of IFN-γ and its receptors in the surface of mononuclear cells to function optimally. The objective of this study is to analyze the correlation of IFNγ serum level, expression and function of IFN-γ receptor, with pulmonary tuberculosis. Analytical descriptive method with cross sectional design that compared the serum level of IFN-γ, function and expression of IFN-γ receptor in pulmonary tuberculosis patients with their healthy spouses, and analyzing the correlation between these variables with pulmonary tuberculosis. Study was done from July 2009 until September 2010, in Immanuel hospital Bandung and Stem Cell & Cancer Institute Jakarta. Compared with their healthy spouses the IFN-γ serum level in TB patients was not different statistically, the IFN-γ receptor expression in TB patients was higher (p=0,041), however, the IFN-γ receptor function of TB patients was lower (p=0,011). Correlation analysis showed that the only variable had correlation significantly with pulmonary tuberculosis was low function of IFN-γ receptor (p=0,026,OR 5,56). The expression of IFN-γ receptor in pulmonary tuberculosis patients was higher, while the function of IFN-γ receptor was lower than their healthy spouses. The low function of IFN-γ receptor had significantly correlation with pulmonary tuberculosis. Key Words: Tuberculosis, IFN-γ serum level, IFN-γ receptor expression and function.

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