High IFN-γ Release and Impaired Capacity of Multi-Cytokine Secretion in IGRA Supernatants Are Associated with Active Tuberculosis

Carrère-Kremer, Séverine; Rubbo, Pierre-Alain; Pisoni, Amandine; Bendriss, Sophie; Marin, Grégory; Peries, Marianne; Bolloré, Karine; Terru, Dominique; Godreuil, Sylvain; Bourdin, Arnaud; Perre, Philippe Van de; Tuaillon, Édouard

doi:10.1371/journal.pone.0162137

Cited by 9 publications

(9 citation statements)

References 34 publications

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“…Another study showed that mycobacterium-specific CD8 þ T cells can secrete IFN-c without help from CD4 þ T cells. 15 Our results are in agreement with those of previous studies, [16][17][18] which indicated that IFN-c release was clearly elevated during MTB infection. Furthermore, we found that 28 pg/mL of IFN-c had advantages over the recommended cut-off value of 14 pg/mL for TB- IGRA.…”

Section: Discussionsupporting

confidence: 91%

Combining interferon-γrelease assays with lymphocyte enumeration for diagnosis ofMycobacterium tuberculosisinfection

Liu

Guo

et al. 2020

J Int Med Res

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Objective To investigate the possibility of combining tuberculosis (TB)-interferon (IFN)-γ release assays (IGRAs) with lymphocyte enumeration for diagnosis of Mycobacterium tuberculosis infection. Methods We performed a retrospective study of 166 TB patients [68 patients with pulmonary tuberculosis TB (PTB) and 98 patients with extra-pulmonary TB (EPTB)] diagnosed in our hospital between January 2016 and May 2018 along with 377 non-TB patients. The diagnostic performance of the TB-IGRA was evaluated using receiver operating characteristic (ROC) curves. Youden’s index was used to determine the optimal cut-off threshold. Results IFN-γ release in patients with PTB and EPTB were dramatically higher compared with non-TB patients (203.58±18.00 pg/mL, 201.83±14.56 pg/mL and 32.12±4.36 pg/mL, respectively). IFN-γ release was positively correlated with lymphocyte counts and percentages in patients with PTB (r = 0.252 and r = 0.278, respectively) and EPTB (r = 0.229 and r = 0.298, respectively). No correlation was observed in non-TB patients. The area under the ROC curve for TB-IGRA was 0.884. When the optimal cut-off value for IFN-γ (14 pg/mL, Youden’s index 0.661) was applied, the sensitivity was 88.6% and the specificity was 77.5%. Conclusions Combining TB-IGRA with lymphocyte enumeration was effective for diagnosis of early-stage Mycobacterium tuberculosis infection.

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Section: Discussionsupporting

confidence: 91%

Combining interferon-γrelease assays with lymphocyte enumeration for diagnosis ofMycobacterium tuberculosisinfection

Liu

Guo

et al. 2020

J Int Med Res

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“…Blood was collected for the IGRA and analyzed with the Quan-tiFERON Gold In-Tube assay (Cellestis/Qiagen, Dusseldorf, Germany). The IGRA method quantifies the IFN-γ released after the incubation of blood with a cocktail of peptides derived from ESAT-6, CFP-10, and TB7.7 (Rv2654c) antigens [24]. The IGRA was considered positive if the level of IFN-γ was 0.35 IU/mL or more [24].…”

Section: Tst and Igramentioning

confidence: 99%

Tuberculin Skin Testing versus Interferon-Gamma Release Assay among Users of a Public Health Unit in Northeast Portugal

Afonso

Pires

Teixeira

et al. 2020

Port J Public Health

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The screening of groups with a high risk for developing tuberculosis (TB) is a priority in order to control this disease. Since there is no gold standard for the diagnosis of latent TB infection (LTBI), both the tuberculin skin test (TST) and the interferon-gamma release assays (IGRA) have been used for this purpose. The aim of this study was to determine the proportion of LTBI by using the TST and the IGRA tests, and to assess the risk factors related with discordant results between tests across several risk groups advised for screening in Northeast Portugal. Data were collected from the database of patients with suspected LTBI and advised for the screening in a public health unit (January 2014 to December 2015). The proportion of LTBI was computed using both tests. Logistic regression models assessed risk factors for a positive test and for discordant results between tests. The adjusted odds ratio (OR) and respective 95% confidence interval (95% CI) were obtained. Out of 367 patients included in the analysis, 79.8% had a positive TST and 46.0% of them had a positive IGRA. In comparison with contacts of active TB cases, healthcare workers and inmates presented higher odds of TST positivity (OR 4.38, 95% CI 1.59–12.09 and OR 4.74, 95% CI 1.45–15.49, respectively), but immunocompromised people presented lower odds of TST positivity (OR 0.14; 95% CI 0.06–0.31). Instead, healthcare workers (OR 0.44, 95% CI 0.24–0.80) and immunocompromised people (OR 0.24, 95% CI 0.10–0.56) presented lower odds of a positive IGRA. There were 42.0% concordant positive results, 16.1% concordant negative results, and 41.9% discordant results, with healthcare workers presenting higher odds of discordant results (OR 3.34, 95% CI 1.84–6.05). The proportion of LTBI estimated by TST and IGRA among people advised for screening in our setting is high, highlighting the need of preventive strategies. Among healthcare workers, TST results should be read with caution as the higher proportion of discordant results with a positive TST suggests the impact of the booster reaction in this group.

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“…Interleukin-2 (IL-2) was the most extensively investigated alternative immunological biomarker (Hur et al, 2015;Wergeland et al, 2016;Won et al, 2017;La Manna et al, 2018;Lesosky et al, 2019). IFN-γ inducible protein or CXCL-10 (IP-10) (Jeong et al, 2015;Wergeland et al, 2016;Villar-Hernández et al, 2017) and monokine induced by IFN-γ or CXCL-9 (MIG) (Frahm et al, 2011;Carrère-Kremer et al, 2016)…”

Section: Introductionmentioning

confidence: 99%

QuantiFERON-TB Gold Plus Assay in Patients With Latent vs. Active Tuberculosis in a Low Incidence Setting: Level of IFN-γ, CD4/CD8 Responses, and Release of IL-2, IP-10, and MIG

et al. 2022

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ObjectivesWe analyzed the results of the QuantiFERON Glod Plus assay (QFT) and cytokine patterns associated with active tuberculosis (ATB) among patients with positive QFT.MethodsA total of 195 patients are QFT-positive, among which 24 had an ATB and 171 had a latent tuberculosis infection (LTBI). Interferon-gamma (IFN-γ) secretion was analyzed relative to interleukin-2 (IL-2), IFN-γ inducible protein or CXCL-10 (IP-10), and monokine induced by IFN-γ or CXCL-9 (MIG) secretion, and then compared between two sets of peptide antigens [tube 1 - cluster of differentiation 4 (CD4+) T cell stimulation; tube 2 - CD4+/CD8+ T cell response].ResultsHigher IFN-γ responses were measured in the ATB group (p = 0.0089). The results showed that there was a lower ratio of tube 1/tube 2 IFN-γ concentrations in the ATB group (p = 0.0009), and a median [interquartile ranges (IQR)] difference between the two sets at −0.82 IU/ml (−1.67 to 0.18) vs. −0.07 IU/ml (−0.035 to 0.11, p < 0.0001) in the ATB group compared to the LTBI group, respectively. In addition, patients with low ratios of IL-2/IFN-γ, IP-10/IFN-γ, and MIG/IFN-γ were much more likely to have ATB.ConclusionHigh levels of IFN-γ secretion, preferential IFN-γ response in tube 2, and lower secretion of IL-2, IP-10, and MIG release relative to IFN-γ secretion were more likely observed in subjects with ATB. These features of T cell response may be helpful in low prevalence settings to suspect ATB in patients tested positive for IFN-γ release assays (IGRA).

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High IFN-γ Release and Impaired Capacity of Multi-Cytokine Secretion in IGRA Supernatants Are Associated with Active Tuberculosis

Cited by 9 publications

References 34 publications

Combining interferon-γrelease assays with lymphocyte enumeration for diagnosis ofMycobacterium tuberculosisinfection

Combining interferon-γrelease assays with lymphocyte enumeration for diagnosis ofMycobacterium tuberculosisinfection

Tuberculin Skin Testing versus Interferon-Gamma Release Assay among Users of a Public Health Unit in Northeast Portugal

QuantiFERON-TB Gold Plus Assay in Patients With Latent vs. Active Tuberculosis in a Low Incidence Setting: Level of IFN-γ, CD4/CD8 Responses, and Release of IL-2, IP-10, and MIG

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