Quantitative scoring of an interferon-γ assay for differentiating active from latent tuberculosis

Jp, Janssens; Roux‐Lombard, Pascale; Perneger, Thomas; Metzger, Marie; Vivien, Régis; Rochat, Thierry

doi:10.1183/09031936.00028507

Cited by 92 publications

(73 citation statements)

References 17 publications

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“…We used ROC curves to evaluate the T-SPOT.TB test, and they showed that the AUC for the T-SPOT.TB test, ESAT-6, and CFP-10 were 0.93, 0.91, and 0.9, respectively, which was higher than those described by Janssens et al and Ling et al (6,10). Our results suggest that the T-SPOT.TB test is a fast and accurate method for the diagnosis of ATB in China.…”

Section: Discussioncontrasting

confidence: 41%

“…It is thought that there is an association between the activity of mycobacteria and the level of interferon gamma secretion and that the interferon gamma level in ATB is significantly higher than that in LTBI. Some authors have suggested that IGRAs have a role in the diagnosis of ATB (4, 5, 9), whereas others object to their use in ATB due to the low specificity (6,10,11). Currently, there are two commercially available IGRAs: QFT-G-IT and T-SPOT.TB.…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of the Characteristics of the Enzyme-Linked Immunospot Assay for Diagnosis of Active Tuberculosis in China

Wang¹,

Yu²,

Chen³

et al. 2015

Clin. Vaccine Immunol.

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bThe purpose of this study was to evaluate the characteristics of the T-SPOT.TB test for the diagnosis of active tuberculosis (ATB) and to distinguish ATB from other diseases using a receiver operating characteristic (ROC) curve. A total of 535 patients with suspected active tuberculosis were enrolled in the study and divided into ATB and nonactive tuberculosis (NATB) groups, as well as pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) subgroups. The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio of the T-SPOT.TB test for the diagnosis of ATB were 84.95%, 85.12%, 82.94%, 86.93%, 5.71, and 0.18, respectively. The median number of spot-forming cells (SFCs) in the ATB group was higher than that in the NATB group (71 versus 1; P < 0.0001). The sensitivities in the PTB and EPTB subgroups were 92.31% and 81.77%. The areas under the curve (AUC) for the diagnosis of ATB using the T-SPOT.TB, early secreted antigenic target 6 (ESAT-6), and culture filtrate protein 10 (CFP-10) were 0.906, 0.884, and 0.877, respectively. A cutoff of 42.5 SFCs for ATB yielded a positive predictive value of 100%. Our study shows that the T-SPOT.TB test is useful for the diagnosis of ATB. Utilizing an ROC curve to select an appropriate cutoff made it possible to discriminate ATB from NATB.T uberculosis is a serious public health issue. Data from 202 countries and territories have shown that approximately 9 million people developed tuberculosis and 1.5 million people died from the disease in 2013 (1). China has the second heaviest burden of tuberculosis in the world, with 1 million new cases of active tuberculosis (ATB) each year and a reported Mycobacterium tuberculosis infection rate of 44.5% (2). The fifth national tuberculosis epidemiological survey in 2010 in China showed that the prevalence of active pulmonary tuberculosis (PTB) was 459/ 100,000 and the prevalence of smear-positive PTB was 66/100,000 in people over 15 years of age (3). At present, routine diagnostic methods for ATB in China include acid-fast bacillus smear, culture, pathology, erythrocyte sedimentation rate (ESR), and the tuberculin skin test (TST). However, as these methods have either low sensitivity or specificity or require a long time to provide a result, their clinical application has been limited.After M. tuberculosis infection, effector T cells targeting M. tuberculosis are generated in peripheral blood mononuclear cells (PBMCs) or body fluid mononuclear cells (MCs). These effector T cells secrete interferon gamma (IFN-␥) when stimulated by specific RD1 antigens, such as early secreted antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10) (4-8), but these RD1 antigens are not present in Mycobacterium bovis bacillus Calmette-Guérin or in most environmental mycobacteria. The T-SPOT.TB test uses ESAT-6 and CFP-10 to stimulate effector T cells in the sample, which then secrete IFN-␥. The cytokine is then captured by specific antibodies in microtit...

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Section: Discussioncontrasting

confidence: 41%

Section: Discussionmentioning

confidence: 99%

Evaluation of the Characteristics of the Enzyme-Linked Immunospot Assay for Diagnosis of Active Tuberculosis in China

Wang¹,

Yu²,

Chen³

et al. 2015

Clin. Vaccine Immunol.

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“…Studies with experimentally infected animals support this possibility (5). Indeed, many studies conducted with IGRAs have shown higher IFN-␥ responses in active TB patients than in LTBI cases (17,73,74,164). Discordant results, however, have also been obtained (113).…”

Section: Cellular Immune Responses and Infection Statementioning

confidence: 68%

Immunodiagnosis of Tuberculosis: a Dynamic View of Biomarker Discovery

Kunnath-Velayudhan¹,

Gennaro²

2011

Clin Microbiol Rev

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SUMMARY Infection with Mycobacterium tuberculosis causes a variety of clinical conditions ranging from life-long asymptomatic infection to overt disease with increasingly severe tissue damage and a heavy bacillary burden. Immune biomarkers should follow the evolution of infection and disease because the host immune response is at the core of protection against disease and tissue damage in M. tuberculosis infection. Moreover, levels of immune markers are often affected by the antigen load. We review how the clinical spectrum of M. tuberculosis infection correlates with the evolution of granulomatous lesions and how granuloma structural changes are reflected in the peripheral circulation. We also discuss how antigen-specific, peripheral immune responses change during infection and how these changes are associated with the physiology of the tubercle bacillus. We propose that a dynamic approach to immune biomarker research should overcome the challenges of identifying those asymptomatic and symptomatic stages of infection that require antituberculosis treatment. Implementation of such a view requires longitudinal studies and a systems immunology approach leading to multianalyte assays.

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“…Existing blood-based tests, such as IFN-γ release assays (IGRAs), measure IFN-γ + production in response to stimulation with Mtb-specific antigens ESAT6 and CFP10 and are specific for Mtb infection (3,4). However, IGRAs (e.g., QuantiFERON or T-SPOT.TB) fail to discriminate between ATB and latent Mtb infection (LTBI) (5,6) and are inadequate for monitoring treatment response (7). Since CD4 + T cells are the predominant cell type producing IFN-γ in response to Mtb infection (8), we hypothesized that host immune markers on Mtb-specific CD4 + T cells that correlate with pathogen load could confer discriminatory capacity to IFN-γ-based assays.…”

Section: Introductionmentioning

confidence: 99%

Biomarkers on patient T cells diagnose active tuberculosis and monitor treatment response

Adékambi¹,

Ibegbu²,

Cagle³

et al. 2015

J. Clin. Invest.

140

189

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Quantitative scoring of an interferon-γ assay for differentiating active from latent tuberculosis

Cited by 92 publications

References 17 publications

Evaluation of the Characteristics of the Enzyme-Linked Immunospot Assay for Diagnosis of Active Tuberculosis in China

Evaluation of the Characteristics of the Enzyme-Linked Immunospot Assay for Diagnosis of Active Tuberculosis in China

Immunodiagnosis of Tuberculosis: a Dynamic View of Biomarker Discovery

Biomarkers on patient T cells diagnose active tuberculosis and monitor treatment response

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