scholarly journals The effect of antituberculosis treatment on interferon-γ release assay results

2015 ◽  
Vol 75 (4) ◽  
Author(s):  
M. Bugiani ◽  
S. Bonora ◽  
A. Carosso ◽  
P. Piccioni ◽  
M. Cavallero ◽  
...  

Background and Aim. Monitoring the efficacy of antituberculosis therapy is crucial. The aim of this work is to investigate the effect of tuberculosis treatment on interferon- γ response using Quanti-FERON©-TB Gold in tube (QFT-GIT). Methods. A total of 216 new pulmonary tuberculosis (TB) cases were tested with QFT-GIT at the start of the treatment and, randomly, once or twice between 90 and 180 days afterwards. Data was analysed using the random effect regression model analysis. Results. 63.4% of patients were positive at the QFTGIT (>.35 UI cut-off). TB cases showed a significant loglinear increase in interferon-γ (IFN-γ) concentration, over time of treatment: IFN-γ concentration increased by 78% after 6 months of treatment in acid-fast bacilli positive (A) and culture negative cases in culture confirmed cases the increase was 43% if A+ and 20% in A-. Conclusions. Effective therapy seems to restore cellular responses to Mycobacterium tuberculosis antigens. The potential use of interferon gamma release assay (IGRA) in monitoring response to TB treatment is hampered by the presence of active mycobacterial replication at baseline and needs further evaluation.

2017 ◽  
Vol 11 (11) ◽  
pp. 847-853 ◽  
Author(s):  
Yu Feng ◽  
Liangquan Zhu ◽  
Xiaowei Peng ◽  
Hui Jiang ◽  
Ge Zhang ◽  
...  

Introduction: Brucellosis, caused by Brucella abortus (B. abortus), is an important zoonosis posing a great risk to both livestock and humans. Currently, most assays for clinical diagnosis of brucellosis have been developed based on serological principles; however, these assays have a number of limitations and disadvantages. Methodology: To address this concern, the aim of this study was to develop a gamma interferon (IFN-γ) release assay (IGRA) for the diagnosis of brucellosis. Towards this end, the stimulating effect induced by different somatic antigens of B. abortus on the secretion of IFN-γ was evaluated. Results: The best antigen candidate, B. abortus strain 2308, able to induce high levels of IFN-γ expression in peripheral blood (PB) cells from cattle, was used for the development of the IGRA. The optimal concentration for stimulation was determined as 1.0×107 CFU/mL. This study demonstrated that IFN-γ was detectable on day 5 post infection (p.i.) and peaked on day 14 p.i.. Finally, the IGRA developed was used for detection of B. abortus in clinical samples, and a higher level of IFN-γ was detected in Brucella-infected samples compared to vaccination samples and negative controls. Conclusions: The optimal somatic antigen for B. abortus was identified and used to establish a robust IGRA. The IGRA developed is suitable for clinical diagnosis of brucellosis, especially in the early stages of infection.


2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Beatriz Oliveira Lopes ◽  
Margarida Sena Brízido ◽  
Ana Isabel Reis ◽  
Margarida Maria Miranda ◽  
Susana Morais Pina

Eales’ disease is a peripheral occlusive retinal phlebitis, with an unclear pathogenesis. The classic association with hypersensitivity to Mycobacterium tuberculosis protein infers that immunologic disturbance may be involved. Here, we described three cases of Eales’ disease. All patients are Caucasian men aged 27-58 years and presented with vitreous hemorrhage and/or peripheral venous vasculitis. Tuberculin skin sensitive test (Mantoux screening test) and interferon-gamma release assay (IGRA) were positive in all patients. Therapeutic approach included antituberculosis therapy and systemic steroids, associated or not to immunosuppressive therapy, and retinal scatter photocoagulation in all cases. Antivascular endothelial grow factor (VEGF) intravitreal injections were also required in two cases. Since various retinal diseases can resemble this presentation, Eales’ disease is considered a diagnosis of exclusion. Early diagnosis and appropriate therapeutic approach are both essential to accomplish disease control and reduce ophthalmologic complications.


2009 ◽  
Vol 16 (8) ◽  
pp. 1170-1175 ◽  
Author(s):  
A. K. Detjen ◽  
L. Loebenberg ◽  
H. M. S. Grewal ◽  
K. Stanley ◽  
A. Gutschmidt ◽  
...  

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.


2021 ◽  
Vol 8 ◽  
Author(s):  
Xiaoyan Gai ◽  
Hongbin Chi ◽  
Lin Zeng ◽  
Wenli Cao ◽  
Lixue Chen ◽  
...  

Introduction: Tuberculosis (TB) is a major infectious disease that seriously endangers human health and female reproduction. In our previous study, 10.4% of infertile patients preparing for In vitro fertilization and embryo transfer (IVF-ET) had prior pulmonary TB (PTB) as detected on chest X-ray (CXR) screening. Among them, 81.8% did not receive anti-TB treatment. It remains unclear whether infertile women with untreated prior PTB have latent TB infection (LTBI) and whether LTBI affects IVF-ET outcomes. In this study, we aim to analyze the relationship between LTBI and pregnancy outcomes following IVF-ET in patients with untreated prior PTB.Methods and Analysis: We designed a prospective cohort study of 1,200 infertile women with CXR findings suggestive of old-healed untreated TB, who are preparing for IVF-ET. Patients with a history of active TB and anti-TB treatment will be excluded. Interferon-gamma release assay (IGRA) will be used in patients with CXR findings suggestive of old-healed untreated TB to construct a cohort of IGRA-positive and IGRA-negative patients. Participants will undergo IVF-ET. General information, including age, body mass index, infertility causes, and controlled ovarian hyperstimulation protocol, will be recorded. Participants will be followed up during pregnancy. The primary outcome is live birth. Secondary outcomes include the numbers of retrieved oocytes, high-quality embryo rate, clinical pregnancy, number of active TB cases during pregnancy, and miscarriage.Ethics and Dissemination: The study was approved by the Ethics Committee of Peking University Third Hospital [approval number (2020)218-01; approval date: June 19, 2020]. The research results will be disseminated through scientific/medical conferences and published in academic journals.Trial Registration:ClinicalTrials.gov; identifier: NCT04443283.


Author(s):  
Sermin Borekci ◽  
Fatma Gulsum Karakas ◽  
Serhat Sirekbasan ◽  
Bahar Kubat ◽  
Rıdvan Karaali ◽  
...  

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.


2009 ◽  
Vol 30 (6) ◽  
pp. 581-584 ◽  
Author(s):  
Priya Khanna ◽  
Vladyslav Nikolayevskyy ◽  
Fiona Warburton ◽  
Elek Dobson ◽  
Francis Drobniewski

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.


Rheumatology ◽  
2020 ◽  
Vol 59 (11) ◽  
pp. 3479-3487 ◽  
Author(s):  
Jenna L Thomason ◽  
Uchechukwu M Obih ◽  
David M Koelle ◽  
Christian Lood ◽  
and Grant Hughes

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.


2019 ◽  
Vol 69 (10) ◽  
pp. 1724-1730 ◽  
Author(s):  
Elisa Nemes ◽  
Deborah Abrahams ◽  
Thomas J Scriba ◽  
Frances Ratangee ◽  
Alana Keyser ◽  
...  

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.


2021 ◽  
Vol 12 ◽  
Author(s):  
Mathis Steindor ◽  
Florian Stehling ◽  
Margarete Olivier ◽  
Jan Kehrmann ◽  
Margo Diricks ◽  
...  

Mycobacterium abscessus complex (MABC) infection has a devastating impact on the course of cystic fibrosis (CF) and non-CF lung disease. Diagnosis of MABC pulmonary disease is challenging, and current diagnostic approaches lack accuracy, especially in CF. In this study, we aimed to establish an MABC-specific interferon-γ release assay to detect host immune responses to MABC and improve diagnostics of MABC infection by the detection of antigen-specific T cells. Four species-specific proteins of MABC were overexpressed in an Escherichia coli expression system. Purified proteins were used to stimulate peripheral blood mononuclear cells of study subjects in an ELISpot assay. Interferon-γ response of 12 subjects with established diagnosis of MABC infection (10 CF and two non-CF) was compared with 35 controls (22 CF and 13 non-CF) distributed to three control groups, 17 CF subjects without NTM infection, nine subjects with NTM infection other than MABC, and nine subjects with tuberculosis. Cellular in vitro responses in the MABC group were stronger than in the control groups, especially toward the protein MAB_0405c (39 vs. 4 spots per 300,000 PBMC, p = 0.004; data represent mean values) in all patients and also in the subgroup of CF subjects (39 spots vs. 1 spot, p = 0.003). Receiver operating characteristic curve analysis indicated that spot numbers of at least 20 were highly predictive of MABC infection (all patients: area under curve 0.773, sensitivity 58%, and specificity 94%; CF patients: area under curve 0.818, sensitivity 60%, and specificity 100%). In conclusion, we identified MAB_0405c as a protein that may stimulate MABC-specific interferon-γ secretion and may add to the diagnosis of MABC infection in affected patients.


2021 ◽  
Author(s):  
Kanagavel Murugesan ◽  
Prasanna Jagannathan ◽  
Jonathan Altamirano ◽  
Yvonne A Maldonado ◽  
Hector F. Bonilla ◽  
...  

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.


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