scholarly journals The Relationship between Pre-Pandemic Interferon Gamma Release Assay Test Results and COVID-19 Infection: Potential Prognostic Value of Indeterminate IFN-γ Release Assay Results

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Sermin Borekci ◽  
Fatma Gulsum Karakas ◽  
Serhat Sirekbasan ◽  
Bahar Kubat ◽  
Rıdvan Karaali ◽  
...  
Keyword(s):  
Interferon Gamma ◽  
Smoking History ◽  
Interferon Gamma Release Assay ◽  
Test Results ◽  
Obstructive Pulmonary Disease ◽  
Igra Test ◽  
Release Assay ◽  
Ifn Γ ◽  
Artery Disease ◽  
The Relationship

Objective. To reveal the relationship between interferon-gamma release assay (IGRA) test (Standard ETB-Feron ELISA (TBF)) results performed within 12 months before the COVID-19 pandemic and the frequency of COVID-19 infections and the severity of COVID-19. Methods. The retrospective TBF test results and contact information of 684 patients aged over 18 years who underwent TBF testing between March 11th, 2019, and March 10th, 2020, were obtained. Of the 684 patients contacted by phone, 365 agreed to participate in the study and were enrolled. The patients were divided into three groups (TBF test positive, negative, and indeterminate). The data obtained from the questionnaire were compared statistically. Results. According to the TBF test results, positive (n = 51, 14%), negative (n = 286, 78.3%), and indeterminate (n = 28, 7.7%) groups were compared. The frequency of COVID-19 infections in the indeterminate group was found significantly higher than that in the positive and negative groups ( p = 0.005 ). When the group with COVID-19 (n = 46, 12.6%) was compared with the group without (n = 319, 87.4%), no difference was found in terms of age, sex, body mass index, smoking history and number of cigarettes smoked, TB history, diabetes mellitus, hypertension, coronary artery disease, and biologic and corticosteroid therapy use. Only the frequency of obstructive pulmonary disease was significantly higher in the group without COVID-19 ( p = 0.033 ). Conclusion. The frequency of COVID-19 infection was increased in patients with indeterminate TBF test results. Indeterminate TBF test results may be a guide in terms of risk stratification in groups at risk for COVID-19.

scholarly journals Safety and Immunogenicity of the GamTBvac, the Recombinant Subunit Tuberculosis Vaccine Candidate: A Phase II, Multi-Center, Double-Blind, Randomized, Placebo-Controlled Study

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 652 ◽  
Author(s):  
Artem P. Tkachuk ◽  
Evgeniia N. Bykonia ◽  
Liubov I. Popova ◽  
Denis A. Kleymenov ◽  
Maria A. Semashko ◽  
...  
Keyword(s):  
Interferon Gamma ◽  
Phase Ii ◽  
Intracellular Cytokine Staining ◽  
Study Drug ◽  
Controlled Study ◽  
Interferon Gamma Release Assay ◽  
Double Blind ◽  
Igra Test ◽  
Th1 Cytokine ◽  
Release Assay

GamTBvac is a candidate tuberculosis vaccine with two fusion proteins, containing Ag85a, ESAT6, CFP10, and a dextran-binding domain (DBD). Phase II of a double-blind, randomized, multicenter, placebo-controlled study in parallel groups in healthy adults to evaluate the safety and immunogenicity of GamTBvac in 180 previously-vaccinated with Bacillus Calmette–Guérin vaccine (BCG) healthy volunteers without Mycobacterium tuberculosis (MTB) infection was conducted. The dose (0.5 mL) of either the study drug or a placebo was administered subcutaneously twice with an 8-week interval. At eight timepoints from 14 to 150 days, whole blood and sera were assayed. Antigen-specific T-cell responses were measured by an in-house interferon-gamma release assay (IGRA-test), the QuantiFERON (QTF) test, and intracellular cytokine staining (ICS). For antibody response detection, the bead-based multiplex immunoassay (MIA) was applied. The vaccine confirmed an acceptable safety profile previously shown in a first-in-human clinical study. After stimulation with both fusions, the highest median level of INF-γ was detected on day 21. The GamTBvac vaccine induced antigen-specific interferon-gamma release, Th1 cytokine-expressing CD4+ T-cells, and IgG responses and results support further clinical testing of GamTBvac.

scholarly journals Short-Term Reproducibility of a Commercial Interferon Gamma Release Assay

2009 ◽  
Vol 16 (8) ◽  
pp. 1170-1175 ◽  
Author(s):  
A. K. Detjen ◽  
L. Loebenberg ◽  
H. M. S. Grewal ◽  
K. Stanley ◽  
A. Gutschmidt ◽  
...  
Keyword(s):  
Interferon Gamma ◽  
Health Care Workers ◽  
Immune Memory ◽  
Interferon Gamma Release Assay ◽  
Short Term ◽  
Care Workers ◽  
Interferon Gamma Release Assays ◽  
Release Assay ◽  
Ifn Γ ◽  
Storage Methods

ABSTRACT Interferon gamma release assays (IGRAs) have been shown to be sensitive and highly specific for the detection of immune memory against Mycobacterium tuberculosis. Little is known about the reproducibility and within-person variability of these assays. Various aspects of short-term reproducibility of a commercial IGRA, the QuantiFERON-TB Gold In-Tube (QFT-IT) assay, were assessed. The QFT-IT assay was performed twice within 3 days in 27 health care workers in Cape Town, South Africa. Two sets of tests were performed by different operators on day 1, and one set was performed on day 3. Aspects such as interoperator, intraoperator, day-to-day variability, and test-retest variability as well as different the storage methods of plasma were investigated. Seventeen of 27 (63%) of participants had at least one positive QFT-IT text; six had discordant results. The agreement of all aspects studied was high, with kappa values between 0.82 and 1.00 for dichotomous measures, and interclass correlations (ICC) of 0.809 to 0.965 were observed for continuous gamma interferon (IFN-γ) measures. The variability of the magnitude of response was highest comparing measures obtained from individuals on different days (ICC of 0.809). The magnitude of the IFN-γ responses between assays performed for individual participants was variable, with ranges from 0.03 to 11 IU/ml, resulting is discordant results for five participants. The results indicate that the QFT-IT assay is a robust and highly reproducible assay. Considerable intraindividual variability occurs in the magnitude of IFN-γ responses, which may influence the interpretation of serial measures.

Diagnosis of latent tuberculosis infection among HIV-infected clients in Far North Queensland: use of an interferon-gamma release assay

Sexual Health ◽  
2013 ◽  
Vol 10 (4) ◽  
pp. 389
Author(s):  
Katrina Lyne ◽  
Sandra Downing ◽  
Darren Russell
Keyword(s):  
Interferon Gamma ◽  
Significant Risk ◽  
Latent Tuberculosis ◽  
Tuberculosis Infection ◽  
Interferon Gamma Release Assay ◽  
Test Results ◽  
Mycobacterium Tuberculosis Infection ◽  
Far North ◽  
Release Assay ◽  
Tuberculosis Risk

Latent Mycobacterium tuberculosis infection is a significant risk for those infected with HIV. We examined the use of an interferon-gamma release assay for the diagnosis of latent tuberculosis among HIV-infected clients attending two sexual health services in Far North Queensland. Of 240 clients tested, 19 returned a positive result (7.9%, 95% confidence interval (CI): 4.5–11.3%) and three were indeterminate (1.3%, 95% CI: –0.2%–2.7%). Low CD4 count was found to be significantly associated with an indeterminate test result (P = 0.004). However, we found no significant association between test results and client demographics, self-reported prior tuberculosis infection, Bacille Calmette-Guérin vaccine status or selected tuberculosis risk factors (P-values = 0.2–0.9).

An interferon-gamma release assay as a novel biomarker in systemic lupus erythematosus

Rheumatology ◽  
2020 ◽  
Vol 59 (11) ◽  
pp. 3479-3487 ◽  
Author(s):  
Jenna L Thomason ◽  
Uchechukwu M Obih ◽  
David M Koelle ◽  
Christian Lood ◽  
and Grant Hughes
Keyword(s):  
Disease Activity ◽  
Lupus Erythematosus ◽  
Ex Vivo ◽  
Peripheral Blood Cell ◽  
Interferon Gamma Release Assay ◽  
Diagnostic Code ◽  
Igra Test ◽  
Cell Release ◽  
Release Assay ◽  
Ifn Γ

Abstract Objective The mycobacterium tuberculosis (TB) IFN-γ release assay (TB-IGRA) assesses peripheral blood cell release of IFN-γ upon ex vivo exposure to mitogen (IGRA-MT), TB antigen or a negative/nil control (IGRA-NL); IGRA-NL is a measure of spontaneous IFN-γ release (SIR). Here, we investigate the diagnostic associations of elevated SIR and the potential use of IGRA-NL as a novel biomarker in SLE. Methods We analysed diagnostic code frequencies among 11 823 individuals undergoing TB-IGRA testing between 2010 and 2015 in a large urban US health-care system. To study the relationship between IGRA-NL and SLE, we identified 99 individuals with SLE and TB-IGRA test results then assessed correlations between IGRA-NL, normalized IGRA-NL (the quotient of IGRA-NL/IGRA-MT), disease manifestations and disease activity. Results We identified a discovery cohort of 108 individuals with elevated SIR (>5 S.d. above median) that was significantly enriched for a limited set of diagnoses, including SLE, TB infection, haemophagocytic lymphohistiocytosis and HIV infection. In SLE patients undergoing TB-IGRA testing, normalized IGRA-NL correlated better with disease activity than did anti-dsDNA or complement levels. This relationship appeared to reflect interactions between normalized IGRA-NL and the presence of acute skin disease, hypocomplementemia, fever and thrombocytopenia. Conclusion Elevated SIR appears to be associated with a limited number of disease processes, including SLE. The diagnostic utility of SIR remains to be determined. IFN-γ activation, as measured by the TB-IGRA test, may offer a readily available tool for assessing disease activity in patients with SLE.

Do higher quantitative interferon gamma release assay or tuberculin skin test results help to predict incident tuberculosis? Data from the UK PREDICT study

2019 ◽  
Author(s):  
Rishi Gupta ◽  
Marc Lipman ◽  
Charlotte Jackson ◽  
Alice Sitch ◽  
Jo Southern ◽  
...  
Keyword(s):  
Tuberculin Skin Test ◽  
Skin Test ◽  
Interferon Gamma ◽  
Interferon Gamma Release Assay ◽  
Test Results ◽  
Release Assay ◽  
The Uk ◽  
Predict Study

scholarly journals Diagnostic Accuracy of Early Secretory Antigenic Target-6–Free Interferon-gamma Release Assay Compared to QuantiFERON-TB Gold In-tube

2019 ◽  
Vol 69 (10) ◽  
pp. 1724-1730 ◽  
Author(s):  
Elisa Nemes ◽  
Deborah Abrahams ◽  
Thomas J Scriba ◽  
Frances Ratangee ◽  
Alana Keyser ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Interferon Gamma ◽  
Blood Collection ◽  
Interferon Gamma Release Assay ◽  
Characteristic Analysis ◽  
Early Secretory Antigenic Target ◽  
Release Assay ◽  
Ifn Γ ◽  
Highly Correlated ◽  
Blood Collection Tubes

Abstract Background Early secretory antigenic target-6 (ESAT-6) is an immunodominant Mycobacterium tuberculosis (M.tb) antigen included in novel vaccines against tuberculosis (TB) and in interferon-gamma (IFN-γ) release assays (IGRAs). Therefore, the availability of an ESAT-6–free IGRA is essential to determine M.tb infection status following vaccination with ESAT-6–containing vaccines. We aimed to qualify a recently developed ESAT-6–free IGRA and to assess its diagnostic performance in comparison to QuantiFERON-TB Gold In-tube (QFT). Methods Participants with different levels of M.tb exposure and TB disease were enrolled to determine the ESAT-6–free IGRA cutoff, test assay performance in independent cohorts compared to standard QFT, and perform a technical qualification of antigen-coated blood collection tubes. Results ESAT-6–free IGRA antigen recognition was evaluated in QFT-positive and QFT-negative South African adolescents. The ESAT-6–free IGRA cutoff was established at 0.61 IU/mL, based on receiver operating characteristic analysis in M.tb-unexposed controls and microbiologically confirmed pulmonary TB patients. In an independent cohort of healthy adolescents, levels of IFN-γ released in QFT and ESAT-6–free IGRA were highly correlated (P < .0001, r = 0.83) and yielded comparable positivity rates, 41.5% and 43.5%, respectively, with 91% concordance between the tests (kappa = 0.82; 95% confidence interval, 0.74–0.90; McNemar test P = .48). ESAT-6–free IGRA blood collection tubes had acceptable lot-to-lot variability, precision, and stability. Conclusions The novel ESAT-6–free IGRA had diagnostic accuracy comparable to QFT and is suitable for use in clinical trials to assess efficacy of candidate TB vaccines to prevent established M.tb infection.

scholarly journals Long Term Accuracy of SARS-CoV-2 Interferon-γ Release Assay and its Application in Household Investigation

2021 ◽  
Author(s):  
Kanagavel Murugesan ◽  
Prasanna Jagannathan ◽  
Jonathan Altamirano ◽  
Yvonne A Maldonado ◽  
Hector F. Bonilla ◽  
...  
Keyword(s):  
Immune Response ◽  
Interferon Gamma ◽  
Post Infection ◽  
Peptide Pool ◽  
Interferon Gamma Release Assay ◽  
Vaccine Response ◽  
Cell Mediated Immune Response ◽  
Release Assay ◽  
Ifn Γ ◽  
Index Cases

AbstractBackgroundAn immunodiagnostic assay that sensitively detects a cell-mediated immune response to SARS-CoV-2 is needed for epidemiological investigation and for clinical assessment of T cell-mediated immune response to vaccines, particularly in the context of emerging variants that might escape antibody responses.MethodsThe performance of a whole blood interferon-gamma (IFN-γ) release assay (IGRA) for the detection of SARS-CoV-2 antigen-specific CD4 and CD8 T cells was evaluated in COVID-19 convalescents tested serially up to 10 months post-infection and in healthy blood donors. SARS-CoV-2 IGRA was applied in contacts of households with index cases. Freshly collected blood in the lithium heparin tube was left unstimulated, stimulated with a SARS-CoV-2 peptide pool, and stimulated with mitogen.ResultsThe overall sensitivity and specificity of IGRA were 84.5% (153/181; 95% confidence interval [CI] 79.0-89.0) and 86.6% (123/142; 95% CI;80.0-91.2), respectively. The sensitivity declined from 100% (16/16; 95% CI 80.6-100) at 0.5-month post-infection to 79.5% (31/39; 95% CI 64.4-89.2) at 10 months post-infection (P<0.01). The IFN-γ response remained relatively robust at 10 months post-infection (3.8 vs. 1.3 IU/mL, respectively). In 14 households, IGRA showed a positivity rate of 100% (12/12) and 65.2% (15/23), and IgG of 50.0% (6/12) and 43.5% (10/23) in index cases and contacts, respectively, exhibiting a difference of +50% (95% CI +25.4-+74.6) and +21.7% (95% CI, +9.23-+42.3), respectively. Either IGRA or IgG was positive in 100% (12/12) of index cases and 73.9% (17/23) of contacts.ConclusionsThe SARS-CoV-2 IGRA is a useful clinical diagnostic tool for assessing cell-mediated immune response to SARS-CoV-2.Key pointsSARS-CoV-2 immunodiagnostics are needed to identify infected individuals in order to understand the transmission dynamics of emerging variants and to assess vaccine response. Interferon-gamma release assay maintains sensitivity 10 months post-infection in convalescents and detects more household contacts than IgG.

An interferon gamma release assay specific for Histoplasma capsulatum to detect asymptomatic infected individuals: A proof of concept study

2018 ◽  
Vol 57 (6) ◽  
pp. 724-732 ◽  
Author(s):  
Marcela Rubio-Carrasquilla ◽  
Cristian David Santa ◽  
Juan Pablo Rendón ◽  
Jorge Botero-Garcés ◽  
Allan J Guimarães ◽  
...  
Keyword(s):  
Risk Factors ◽  
Interferon Gamma ◽  
Histoplasma Capsulatum ◽  
Screening Method ◽  
High Sensitivity ◽  
Positive Control ◽  
Interferon Gamma Release Assay ◽  
Predictive Values ◽  
Release Assay ◽  
Ifn Γ

AbstractHistoplasmosis is the most common endemic mycosis in the Americas. Currently, there is no laboratory test capable to detect subclinical or latent infections by Histoplasma capsulatum (Hc), which might develop as severe infections in immunocompromised individuals. For the first time to our knowledge, we explore the suitability of an interferon gamma release assay (IGRA) to detect latent Hc infection in asymptomatic individuals. A cohort of 126 volunteers was enrolled in the study, 13 of which underwent a Hc infection in the past, and 93 of them showing risk factors for this infection. The remaining 20 participants did not refer any risk factors of Hc infection, but eight of them showed evidences of infection with Mycobacterium tuberculosis. All participants were recruited in Medellin, Colombia, between January 2014 and December 2017. Whole blood samples were cultured with four different Hc crude antigens and phytohemaglutinin as positive control. The interferon (IFN)-γ released by T lymphocytes upon antigen stimulation was quantified by ELISA. A defined cutoff value of 20 pg/ml for the IFN-γ concentration allowed us to distinguish between the group with documented past infections and the group of noninfected individuals with high sensitivity (70–92%) and specificity (85–95%), for the four tested antigens. Positive 82–95% and negative 77–92% predictive values were also very high, comparable to those reported for commercially available IGRAs. The new test constitutes a promising screening method to detect individuals with latent Hc infection, even decades after the primary infection, as evidenced in this study.

The impact of borderline Quantiferon-Plus results for latent tuberculosis screening under routine conditions in a low endemic setting

2021 ◽  
Author(s):  
A Wikell ◽  
J Jonsson ◽  
R Dyrdak ◽  
A. J. Henningsson ◽  
A Eringfält ◽  
...  
Keyword(s):  
Interferon Gamma ◽  
Latent Tuberculosis ◽  
Interferon Gamma Release Assay ◽  
Test Results ◽  
Tuberculosis Screening ◽  
Endemic Setting ◽  
Clinical Laboratories ◽  
Release Assay ◽  
The Impact

Quantiferon-TB Gold Plus (QFT-Plus) is an interferon gamma release assay used to diagnose latent tuberculosis (LTB). A borderline range (0.20-0.99 IU/mL) around the cut off (0.35 IU/ml) has been suggested for the earlier QFT version. Our aims were to evaluate the borderline range for QFT-Plus and the contribution of the new TB2 antigen tube. QFT-Plus results were collected from clinical laboratories in Sweden and linked to incident active TB within 3-24 months using the national TB registry. Among QFT-Plus results from 58539 patients, 83% were negative (<0.20 IU/ml), 2.4% borderline negative (0.20-0.34 IU/ml), 3.4% borderline positive (0.35-0.99 IU/ml), 9.6% positive (≥1.0 IU/ml) and 1.6% indeterminate. Follow-up tests after initial borderline results were negative (<0.20 IU/ml) in 38.3% without any cases of incident active TB within 2 years. Applying the 0.35 IU/ml cut-off, 1.5% of TB1 and TB2 results were discrepant whereof 52% within borderline range. A TB2≥0.35 IU/ml with TB1<0.20 IU/ml was found in 0.4% (231/58539) of all included baseline QFT-Plus test results, including 1.8% (1/55) of incident TB cases. A borderline range for QFT-Plus is clinically useful as more than one third of those with borderline results are convincingly negative upon retesting, without developing incident active TB. The TB2 tube contribution for LTB diagnosis appears limited.

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