Analysis of Factors Influencing Diagnostic Accuracy of T-SPOT.TB for Active Tuberculosis in Clinical Practice

Zhang, Lifan; Shi, Xiaochun; Zhang, Yueqiu; Zhang, Yao; Huo, Feifei; Zhou, Binghua; Deng, Guohua; Liu, Xiaoqing

doi:10.1038/s41598-017-07785-6

Cited by 12 publications

(11 citation statements)

References 25 publications

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“…TB ESAT-6 and CFP-10 responses. Previous studies had determined that the diagnostic efficacy of IGRAs was lower for elderly patients, [ 32 , 33 ] due to their decreased lymphocyte counts and weakened immune function that dampened production of MTB-specific IFN-γ and thus reduced IGRAs sensitivity. [ 33 ] Furthermore, elderly patients are often concomitantly afflicted with several diseases that may increase the complexity of their immune responses.…”

Section: Discussionmentioning

confidence: 99%

Factors associated with differential T cell responses to antigens ESAT-6 and CFP-10 in pulmonary tuberculosis patients

Liu

Wu²,

Ertai³

et al. 2021

Medicine

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The T-SPOT.TB assay detects cellular immune responses to 2 core Mycobacterium tuberculosis antigens, early secreted antigenic target of 6-kDa protein (ESAT-6) and culture filtrate protein-10 (CFP-10). T-SPOT.TB has been recently used for auxiliary diagnosis of active pulmonary tuberculosis (PTB). However, testing can produce inconsistent results due to differential PTB patient immune responses to these antigens, prompting us to identify factors underlying inconsistent results. Data were retrospectively analyzed from 1225 confirmed PTB patients who underwent T-SPOT.TB testing at 5 specialized tuberculosis hospitals in China between December 2012 and November 2015. Numbers of spot-forming cells (SFCs) reflecting T cell responses to ESAT-6 and CFP-10 antigens were recorded then analyzed via multivariable logistic regression to reveal factors underlying discordant T cell responses to these antigens. The agreement rate of 84.98% (82.85%–86.94%) between PTB patient ESAT-6 and CFP-10 responses demonstrated high concordance. Additionally, positivity rates were higher for ESAT-6 than for CFP-10 (84.8% vs 80.7%, P < .001), with ESAT-6 and CFP-10 microwell SFC numbers for each single positive group not differing significantly (P > .99), while spot numbers of the single positive group were lower than numbers for the double positive group (P < .001). Elderly patients (aged ≥66 years) and patients receiving retreatment were most likely to have discordance results. ESAT-6 promoted significantly more positive T-SPOT.TB results than did CFP-10 in PTB patients. Advanced age and retreatment status were correlated with discordant ESAT-6 and CFP-10 results. Assessment of factors underlying discordance may lead to improved PTB diagnosis using T-SPOT.TB.

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Section: Discussionmentioning

confidence: 99%

Factors associated with differential T cell responses to antigens ESAT-6 and CFP-10 in pulmonary tuberculosis patients

Liu

Wu²,

Ertai³

et al. 2021

Medicine

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“…Although Xpert MTB/RIF can detect MTB and rifampin-resistance mutations in several hours with high accuracy, it is estimated that 30–50% patients failed to provide appropriate samples for the test [ 12 ]. Our previous study showed that less than 30% of patients diagnosed with ATB could be confirmed by etiology [ 13 ]. Thus, clinicians urgently need new methods to help diagnose TB, especially for patients who cannot obtain evidence of the pathogens.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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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.

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“…Jeon et al compared different age groups showing that the risk of false negative T-SPOT assay increased 10% [12]. A possible reason could be that the cellular immune response induced by M. tuberculosis specific antigens gradually weakens, leading to a downward trend in the IFN-γ concentration with increasing age [6,13,14]. In addition, elder patients with concomitant diseases and malnutrition status have been reported to lead false negative rate due to a greatly reduced immune response [15].…”

Section: Discussionmentioning

confidence: 99%

“…Its unsatisfactory sensitivity may impact on interpreting IGRA results in highly suspicious TB patients. Previous studies have suggested that immunosuppression, underweight, older age, lymphocytopenia, HIV co-infection, and tuberculous meningitis were associated with false-negative T-SPOT.TB results in different clinical settings [6][7][8][9]. These inadequate studies had small sample sizes or were conducted in settings with varied burdens of disease.…”

Section: Introductionmentioning

confidence: 99%

Risk factors for negative T-SPOT.TB assay results in patients with confirmed active tuberculosis: A retrospective study

Shangguan

Fang

Wang

et al. 2020

J Infect Dev Ctries

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Introduction: The interferon-γ release assays as potent adjunct tools for the quick detection of TB in high burden countries is feasible. In this retrospective study, we aimed to identify the risk factors for negative T-SPOT results in confirmed active tuberculosis. Methodology: We consecutively enrolled 1,021 patients who were positive for acid-fast bacilli smear staining or culture-confirmed mycobacterial infection and simultaneously tested with the T-SPOT.TB assay. All of the included specimens were used to discriminate the Mycobacterium species using the biochip assay. We collected basic clinical characteristics and laboratory results for further analysis. Results: Of the 1,021 patients enrolled in the study, 89 patients were identified as having nontuberculous mycobacteria (NTM). Ninety-nine patients were excluded from the analysis because of indeterminate T-SPOT.TB results, while the remaining 833 patients were identified as having Mycobacterium tuberculosis infection. In total, 159 patients had false-negative T-SPOT.TB results (19.1% of 833). The concordance rate between the T-SPOT.TB results and final diagnoses in females was always lower than that in males. Multivariate logistic regression analysis showed that female sex (OR 1.81; 95% CI 1.19, 2.7; p = 0.006), age (OR 1.02; 95% CI 1.01, 1.03; p = 0.003), acid-fast bacilli (AFB) smear-negative (OR 5.45; 95% CI 3.62, 8.19; p < 0.001), HIV coinfection (OR 6.83; 95% CI 2.73, 17.10; p < 0.001) were associated with negative T-SPOT.TB result. Conclusions: Female is another independent risk factor of negative T-SPOT.TB results, besides to elder, HIV co-infection, acid-fast bacilli (AFB) smear-negative who are suspected of having active TB infection.

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Analysis of Factors Influencing Diagnostic Accuracy of T-SPOT.TB for Active Tuberculosis in Clinical Practice

Cited by 12 publications

References 25 publications

Factors associated with differential T cell responses to antigens ESAT-6 and CFP-10 in pulmonary tuberculosis patients

Factors associated with differential T cell responses to antigens ESAT-6 and CFP-10 in pulmonary tuberculosis patients

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

Risk factors for negative T-SPOT.TB assay results in patients with confirmed active tuberculosis: A retrospective study

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