The conundrum of indeterminate QuantiFERON-TB Gold results before  anti-tumor necrosis factor initiation

Hakimian, Shahrad; Popov, Yevgeniy; Rupawala, Abbas; Salomon-Escoto, Karen; Hatch, Steven C.; Pellish, Randall

doi:10.2147/btt.s150958

Cited by 12 publications

(14 citation statements)

References 29 publications

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“…All but one of the indeterminate QuantiFERON ® results were due to an inadequate immune response, suggesting that it is the immunosuppressive therapy leading to the indeterminate results rather than the acute flare itself. These findings are in keeping with other key studies [ 13 , 14 ]. In our centre, QuantiFERON ® TB Gold In-Tube takes, on average, 2–3 days to return a result; therefore, it can result in significant treatment delays.…”

Section: Discussionsupporting

confidence: 93%

“…In the general population, studies show rates of indeterminate results of 3.8% (8). However, two separate studies in populations with IBD, who were tested prior to initiation of anti-TNFα, showed indeterminate results in 19.5% and 22% of the population [ 13 , 14 ], where authors found corticosteroid use and hospitalization were risk factors associated with an indeterminate result.…”

Section: Discussionmentioning

confidence: 99%

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Screening for TB in Hospitalised Patients with Inflammatory Bowel Disease before Anti-TNF Therapy: Is QuantiFERON® Gold Testing Useful?

Lovatt

Gascoyne-Binzi

Hussey

et al. 2021

JCM

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Background—Tumour necrosis factor alpha (TNFα) plays an important role in the pathogenesis of inflammatory bowel disease (IBD) and in immunity to Mycobacterium tuberculosis. Patients should be tested for latent tuberculosis infection using interferon-gamma release assays (IGRA/QF) prior to anti-TNFα therapy. Indeterminate QF results can delay anti-TNFα therapy. We sought to investigate factors associated with indeterminate QF results. Method—Retrospective study of all IGRA tests requested for gastroenterology patients in 2017. We compared inpatients and outpatients and investigated factors potentially associated with QF usefulness (steroid exposure, C-reactive protein (CRP), hypoalbuminaemia, thrombophilia). Results—We included 286 outpatients and 74 inpatients with IBD. Significantly more inpatients had an indeterminate IGRA (52.7% vs. 3.14% in outpatients; p < 0.0001). Laboratory parameters reflecting inflammation (high CRP, low albumin, low haemoglobin and high platelets) were also associated with an indeterminate QF (p < 0.0001). Exposure to steroids was more common in patients with an indeterminate QF (p < 0.0001). A binary logistic regression analysis revealed inpatient status and steroid exposure to be independently predictive of an indeterminate QF (p < 0.0001). Conclusion—There is a high chance of indeterminate QF results in inpatients. QF testing should ideally be performed in the outpatient setting at diagnosis.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Screening for TB in Hospitalised Patients with Inflammatory Bowel Disease before Anti-TNF Therapy: Is QuantiFERON® Gold Testing Useful?

Lovatt

Gascoyne-Binzi

Hussey

et al. 2021

JCM

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“…Additionally, the QFT-Plus assay includes a mitogen-based control designed to nonspecifically elicit a T-cell response and thus infer the immunological fitness of the studied individuals. It is well known that active inflammation or immunosuppressive drug use is associated with QFT-Plus indeterminate results [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Clinical Significance of Indeterminate QuantiFERON-TB Gold Plus Assay Results in Hospitalized COVID-19 Patients with Severe Hyperinflammatory Syndrome

Solanich

Fernández-Huerta

Basaez³

et al. 2021

JCM

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Performance of the QuantiFERON-TB Gold Plus (QFT-Plus) assay could be affected by conditions of immune dysregulation. Little is known about the reliability of QTF-Plus in COVID-19 patients. Our aim was to determine the prevalence and the factors related to an indeterminate QFT-Plus test in COVID-19 hospitalized patients, and to analyze its relationship with in-hospital mortality. A retrospective analysis of all hospitalized COVID-19 patients on whom a QTF-Plus assay was performed in a tertiary care public hospital during the first epidemic wave in Spain (March–April 2020). Out of a total of 96 patients included, 34 (35.4%) had an indeterminate result, in all cases due to a lack of response in the mitogen control. Factors related to COVID-19 severity, such as higher lactate dehydrogenase (LDH) (odds ratio [OR] 1.005 [95% confidence interval [CI] 1.002–1.008]) and previous administration of corticosteroids (OR 4.477 [95% CI 1.397–14.345]), were independent predictors for indeterminate QFT-Plus assay. Furthermore, indeterminate results were more frequent among COVID-19 patients who died during hospitalization (29.1% vs. 64.7%; p = 0.005). We conclude that QFT-Plus assay yielded an unexpected, high prevalence of indeterminate results in severe COVID-19 patients. Factors related to worse COVID-19 outcome, such as LDH, as well as corticosteroid use before the QFT-Plus assay, seem to be predictors for an indeterminate result. The role of an indeterminate QFT-Plus result in predicting COVID-19 severity and mortality should be evaluated.

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“…27 The results indicate that TB infection may be more difficult to detect in this group compared to other groups. 31,32 Many studies have revealed that high SLEDAI scores are related to more severe symptoms, poor haematology and immunology features and a high probability of indeterminate results. 30,33 Similarly, our study revealed that, compared with other groups, the active group has the lowest IFN-γ level, which reflects an abnormality of the immune response.…”

Section: Discussionmentioning

confidence: 99%

<p>Activity Disease in SLE Patients Affected IFN-γ in the IGRA Results</p>

Maharani¹,

Ratnaningsih²,

Utami³

et al. 2020

JIR

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Purpose: Highly active systemic lupus erythematosus (SLE) causes a high risk of tuberculosis (TB) infection in SLE patients in Indonesia, a country in which the disease, especially extrapulmonary TB, is endemic. Interferon (IFN)-γ releasing assay (IGRA) can detect latent or previous TB infection. This study sought to determine latent TB infection and levels of IFN-γ, a key player in various inflammation and autoimmune disease, in patients with SLE and relate findings to disease activity. Patients and Methods: This experimental study included 79 female subjects distributed into three groups of active SLE, quiescent SLE and healthy controls. We used SLE Disease Activity Index-2000 (SLEDAI-2K) scores to stratify the subjects. Each group underwent IGRA testing using the QuantiFERON-TB Gold Plus kit. Results: We recruited 59 female patients with SLE. The patients had a median age and disease duration 30 and 5 years, respectively. Statistical analysis using the Kruskal-Wallis test showed that active condition, high SLEDAI-2K score and immunosuppressive therapies affect IGRA results. Specifically, healthy controls (n=20) were most likely to have negative IGRA results (67.09%), whilst 27.27% of active cases (n=33) and 3.85% of quiescent cases (n=26) had indeterminate results (p=0.02). The number of immunosuppressant therapies was significantly negatively correlated with IFN-γ (p=0.004). No difference in IFN-γ concentration was detected amongst the active and other groups (p>0.05). Conclusion: High-activity SLE and immunosuppressive therapies cause dysregulation of the immune response, which, in turn, influences IGRA results. Thus, additional testing is necessary to detect TB infection in patients with SLE.

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The conundrum of indeterminate QuantiFERON-TB Gold results before anti-tumor necrosis factor initiation

Cited by 12 publications

References 29 publications

Screening for TB in Hospitalised Patients with Inflammatory Bowel Disease before Anti-TNF Therapy: Is QuantiFERON® Gold Testing Useful?

Screening for TB in Hospitalised Patients with Inflammatory Bowel Disease before Anti-TNF Therapy: Is QuantiFERON® Gold Testing Useful?

Clinical Significance of Indeterminate QuantiFERON-TB Gold Plus Assay Results in Hospitalized COVID-19 Patients with Severe Hyperinflammatory Syndrome

<p>Activity Disease in SLE Patients Affected IFN-γ in the IGRA Results</p>

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