Comparison of IFN-γ Levels in Children with Tuberculosis Disease (TB) and Latent Tuberculosis Infection (LTBI)

AIM: This study aimed to evaluate the importance of IFN-γ in the diagnosis of pediatric TB and LTBI and to compare the IFN-γ levels. METHODS: We analysed 100 patients examined for possible M. tuberculosis infection or disease at the Institute of Respiratory Diseases in Children, Kozle, Skopje. Patients were divided into 2 groups: TB disease and LTBI. The following parameters were analyzed: demographic characteristics, history of previous exposure to active TB, BCG vaccination and presence of BCG scar, lung X-ray findings, tuberculin skin test by the Monteux method and the value of INF -γ according to the Quantiferon TB gold test, direct samples of acid-alcohol-resistant bacilli of sputum and Löwenstein Jensen cultures. Informed parental consent was obtained for each child included in the study. RESULTS: In the LTBI group 60.9% had a scar from the vaccination while in the TB group 50% had BCG scar. TST induration diameters in children with or without BCG scar were significantly larger in patients with active TB. Children with active TB had significantly higher IFN-γ levels than children with LTBI. The IFN-γ for the cut-off of 0.35 IU/ml, has 64% sensitivity for detection of LTBI, versus 80.6% sensitivity for active disease. Children with close TB contact had significantly higher IFN-γ levels. Correlation between TST induration diameter and IFN-γ levels was stronger in the TB group. CONCLUSION: IFN-γ levels are significantly higher in children with active TB, and children with close contact with TB patient. It has better sensitivity in active TB. Using both tests (IFN-γ and TST) can improve the diagnose of LTBI and TB in countries where vaccination with BCG is widespread.

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Screening toll-like receptor markers to predict latent tuberculosis infection and subsequent tuberculosis disease in a Chinese population

BMC Medical Genetics ◽

10.1186/s12881-015-0166-1 ◽

2015 ◽

Vol 16 (1) ◽

Cited By ~ 23

Author(s):

Linlin Wu ◽

Yi Hu ◽

Dange Li ◽

Weili Jiang ◽

Biao Xu

Keyword(s):

Chinese Population ◽

Latent Tuberculosis Infection ◽

Latent Tuberculosis ◽

Tuberculosis Infection ◽

Toll Like Receptor ◽

Tuberculosis Disease

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IFN-γ Release Assays in the Diagnosis of Latent Tuberculosis Infection among Immunocompromised Adults

American Journal of Respiratory and Critical Care Medicine ◽

10.1164/rccm.201209-1621ci ◽

2013 ◽

Vol 188 (4) ◽

pp. 422-431 ◽

Cited By ~ 61

Author(s):

Gil Redelman-Sidi ◽

Kent A. Sepkowitz

Keyword(s):

Latent Tuberculosis Infection ◽

Latent Tuberculosis ◽

Tuberculosis Infection ◽

Ifn Γ

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Heparin-Binding Hemagglutinin Induces IFN-γ+IL-2+IL-17+Multifunctional CD4+T Cells during Latent but Not Active Tuberculosis Disease

Clinical and Vaccine Immunology ◽

10.1128/cvi.00047-12 ◽

2012 ◽

Vol 19 (5) ◽

pp. 746-751 ◽

Cited By ~ 16

Author(s):

André G. Loxton ◽

Gillian F. Black ◽

Kim Stanley ◽

Gerhard Walzl

Keyword(s):

T Cells ◽

Immune Responses ◽

Culture Supernatant ◽

Interleukin 2 ◽

Latent Tuberculosis ◽

Hiv Positive ◽

Heparin Binding ◽

Household Contacts ◽

Ifn Γ ◽

Tuberculosis Disease

ABSTRACTThe mycobacterial heparin-binding hemagglutinin (HBHA) protein induces a potent gamma interferon (IFN-γ) response in latent tuberculosis (TB) infection and is a candidate vaccine and diagnostic antigen. We have assessed HBHA-specific intracellular IFN-γ, interleukin-2 (IL-2), and IL-17 production by CD4+T cells in TB cases and household contacts (HHCs) as well as the level of secreted IFN-γ in whole-blood culture supernatant. HHCs were further classified as tuberculin skin test (TST) positive or negative, and the group was also divided as HIV positive or negative. Our study revealed that HBHA induces multifunctional IFN-γ-, IL-2-, and IL-17-coexpressing CD4+T cells in HHCs but not in active TB cases; however, IFN-γ levels in culture supernatant did not differ between participant groups. Further studies are needed to completely understand how HBHA induces immune responses in different disease groups.

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The Dynamic Change of Immune Checkpoints and CD14+ Monocytes in Latent Tuberculosis Infection

Biomedicines ◽

10.3390/biomedicines9101479 ◽

2021 ◽

Vol 9 (10) ◽

pp. 1479

Author(s):

Ping-Huai Wang ◽

Ming-Fang Wu ◽

Chi-Yu Hsu ◽

Shu-Yung Lin ◽

Ya-Nan Chang ◽

...

Keyword(s):

Mononuclear Cells ◽

Latent Tuberculosis Infection ◽

Dynamic Change ◽

Latent Tuberculosis ◽

Immune Defense ◽

Tuberculosis Infection ◽

Immune Checkpoints ◽

Peripheral Blood Mononuclear ◽

Ltbi Treatment ◽

Ltbi Group

Controlling latent tuberculosis infection (LTBI) is important for preventing tuberculosis (TB). However, the immune regulation of LTBI remains uncertain. Immune checkpoints and CD14+ monocytes are pivotal for immune defense but have been scarcely studied in LTBI. We prospectively enrolled participants with LTBI and controls from January 2017 to December 2019. We measured their CD14+ monocytes and the expression of immune checkpoints, including programmed death-1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and T cell immunoglobulin mucin domain-containing-3 (TIM3) on T lymphocytes in peripheral blood mononuclear cells before and after LTBI treatment. A total of 87 subjects were enrolled, including 29 IGRA-negative healthy controls (HC), 58 in the LTBI group (19 without chronic kidney disease (non-CKD), and 39 with end-stage renal disease (ESRD)). All PD-1, CTLA-4, and TIM3 on lymphocytes and monocytes were higher in the LTBI group than that in the HC group. Total CD14+ monocytes were higher and PD-L2+CD14+ over monocytes were lower in patients with LTBI-non-CKD than that in the HC group. After LTBI treatment, CD14+ monocytes, TIM3+ on CD4+ and monocytes, and CTLA-4 on lymphocytes decreased significantly. Multivariable logistic regression indicated that CD14+ monocytes was an independent factor for LTBI-non-CKD from the HC group, whereas PD-L2+CD14+ monocytes and TIM3+ monocytes were significant for LTBI-ESRD from the HC group. In conclusion, LTBI status was associated with increasing CD14+ monocytes plus low PD-L2 expression. By contrast, increased expression of immune checkpoints over all immune cells might be due to Mycobacterium tuberculosis related immune exhaustion, which decreased after treatment.

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Vitamin D and LL-37 Levels in Childhood Tuberculosis Disease and Latent Tuberculosis Infection

Turkish Thoracic Journal ◽

10.5152/turkthoracj.2019.130 ◽

2019 ◽

Vol 20 (-1) ◽

pp. 130-130

Author(s):

Ebru Yalcin ◽

◽

Nagehan Emiralioglu ◽

Gokcen Dilsa Tugcu ◽

Sanem Eryilmaz ◽

...

Keyword(s):

Vitamin D ◽

Latent Tuberculosis Infection ◽

Latent Tuberculosis ◽

Childhood Tuberculosis ◽

Tuberculosis Infection ◽

Tuberculosis Disease

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A transcriptional blood signature distinguishes early tuberculosis disease from latent tuberculosis infection and uninfected individuals in a Vietnamese cohort

Journal of Infection ◽

10.1016/j.jinf.2020.03.066 ◽

2020 ◽

Vol 81 (1) ◽

pp. 72-80

Author(s):

Jennifer Ho ◽

Nilesh J. Bokil ◽

Phuong Thi Bich Nguyen ◽

Thu Anh Nguyen ◽

Michael Y. Liu ◽

...

Keyword(s):

Latent Tuberculosis Infection ◽

Latent Tuberculosis ◽

Tuberculosis Infection ◽

Tuberculosis Disease

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Vitamin D and LL-37 Levels In Childhood Tuberculosis Disease and Latent Tuberculosis Infection

10.1183/13993003.congress-2019.pa984 ◽

2019 ◽

Author(s):

Ebru Yalçın ◽

Nagehan Emiralioğlu ◽

Gokcen Tuğcu ◽

Sanem Eryılmaz ◽

Mina Hızal ◽

...

Keyword(s):

Vitamin D ◽

Latent Tuberculosis Infection ◽

Latent Tuberculosis ◽

Childhood Tuberculosis ◽

Tuberculosis Infection ◽

Tuberculosis Disease

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Rate of Latent Tuberculosis Infection Detected by Occupational Health Screening of Nurses New to a London Teaching Hospital

Infection Control and Hospital Epidemiology ◽

10.1086/597546 ◽

2009 ◽

Vol 30 (6) ◽

pp. 581-584 ◽

Cited By ~ 13

Author(s):

Priya Khanna ◽

Vladyslav Nikolayevskyy ◽

Fiona Warburton ◽

Elek Dobson ◽

Francis Drobniewski

Keyword(s):

Tuberculin Skin Test ◽

Skin Test ◽

Latent Tuberculosis Infection ◽

Latent Tuberculosis ◽

Interferon Γ ◽

Tuberculosis Infection ◽

Release Assay ◽

Ifn Γ ◽

Positive Results ◽

Tuberculosis Prevalence

The prevalence of latent tuberculosis infection in a cohort of nurses new to a London hospital was 7.6% (13 of 171), using an interferon-γ(IFN-γ) release assay, and 16.2% (24 of 148), using the tuberculin skin test. On multivariate analysis, birth in a country with tuberculosis prevalence of more than 40 cases per 100,000 population was associated with positive results of both the IFN-γ release assay and the tuberculin skin test.

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Evaluation of cytokines as a biomarker to distinguish active tuberculosis from latent tuberculosis infection: a diagnostic meta-analysis

BMJ Open ◽

10.1136/bmjopen-2020-039501 ◽

2020 ◽

Vol 10 (10) ◽

pp. e039501

Author(s):

Beibei Qiu ◽

Qiao Liu ◽

Zhongqi Li ◽

Huan Song ◽

Dian Xu ◽

...

Keyword(s):

Latent Tuberculosis Infection ◽

Meta Analysis ◽

Latent Tuberculosis ◽

Active Tuberculosis ◽

Tuberculosis Infection ◽

Cochrane Library ◽

Effective Vaccine ◽

Specific Method ◽

Case Control Studies ◽

Ifn Γ

ObjectivesWith a marginally effective vaccine and no significant breakthroughs in new treatments, a sensitive and specific method to distinguish active tuberculosis from latent tuberculosis infection (LTBI) would allow for early diagnosis and limit the spread of the pathogen. The analysis of multiple cytokine profiles provides the possibility to differentiate the two diseases.DesignSystematic review and meta-analysis.Data sourcesPubMed, Cochrane Library, Clinical Key and EMBASE databases were searched on 31 December 2019.Eligibility criteriaWe included case–control studies, cohort studies and randomised controlled trials considering IFN-γ, TNF-α, IP-10, IL-2, IL-10, IL-12 and VEGF as biomarkers to distinguish active tuberculosis and LTBI.Data extraction and synthesisTwo students independently extracted data and assessed the risk of bias. Diagnostic OR, sensitivity, specificity, positive and negative likelihood ratios and area under the curve (AUC) together with 95% CI were used to estimate the diagnostic value.ResultsOf 1315 records identified, 14 studies were considered eligible. IL-2 had the highest sensitivity (0.84, 95% CI: 0.72 to 0.92), while VEGF had the highest specificity (0.87, 95% CI: 0.73 to 0.94). The highest AUC was observed for VEGF (0.85, 95% CI: 0.81 to 0.88), followed by IFN-γ (0.84, 95% CI: 0.80 to 0.87) and IL-2 (0.84, 95% CI: 0.81 to 0.87).ConclusionCytokines, such as IL-2, IFN-γ and VEGF, can be utilised as promising biomarkers to distinguish active tuberculosis from LTBI.PROSPERO registration numberCRD42020170725.

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