Adapted T Cell Interferon-Gamma Release Assay for the Diagnosis of Pleural Tuberculosis

Abstract

Background: Better and more rapid tests are needed for the diagnosis of tuberculous pleural effusion (TPE), given the known limitations of conventional diagnostic tests. Objectives: To estimate diagnostic accuracy of the QuantiFERON-TB Gold In-Tube (QFT-GIT) test (and its components) using data-derived cutoffs in pleural fluid. Methods: The QFT-GIT test was performed on whole blood and pleural fluid from 43 patients with TPE and 29 control subjects (non-TPE). To achieve the objective, QFT-GIT test, estimating likelihood ratios and receiver operating curve analysis were performed. Results: The sensitivity and specificity using the QFT-GIT for the diagnosis of TPE were 48.8% and 79.3%, respectively, in pleural fluid. The best cutoff points for tuberculosis (TB) antigen, nil and TB antigen minus nil results were estimated at 0.70, 0.90 and 0.30 IU/ml, respectively. Area under the curve of TB antigen IFN-γ response was 0.86 (CI: 0.76–0.93), nil tube was 0.80 (CI: 0.69–0.89) and TB antigen minus nil tube was 0.82 (CI: 0.72–0.90). When the best cutoff scores of the nil tubes were set at this value, the results of a likelihood ratio of a positive and a negative test were 9.44 (7.4–12.0) and 0.37 (0.09–1.5), respectively. The percentages of indeterminate results in pleural fluid among the TPE cases were 42% (most of them caused by high nil IFN-γ values) using the QFT-GIT test. Conclusion: QFT-GIT test or its components have poor accuracy in the diagnosis of TPE, largely because of a high number of indeterminate results due to high background IFN-γ production in the TPE.

Clinical Utility of Two Interferon-gamma Release Assays on Pleural Fluid for the Diagnosis of Tuberculous Pleurisy

“…First, the T-SPOT.TB assay but not the QFT test requires a mandatory number of mononuclear cells, which might ensure a more accurate result even in patients with low T cell titers, such as those with HIV infection or another immunodeficiency. Second, more accurate results may be obtained when performing the IGRA in PF, the active infection site of tuberculous pleurisy, because of the compartmentalization of the immune response of Th1 cells in TB infection12,16-18,22. Third, in our study, the QFT-G test had more indeterminate interpretations than the T-SPOT.TB test in both PF and blood, which might reduce its diagnostic accuracy.…”

“…Comparing the diagnostic performance of either IGRA between PF and blood samples in the TB pleurisy, some clinical studies showed inconsistent results, depending on the type of assay, patient population, and incidence of TB infection12,15-20. In countries with a low TB burden, the IGRA has superior diagnostic accuracy in PF than in blood, whereas the reverse is true in intermediate-to high-burden countries19,20.…”

“…PF, pleural tissue, and sputum specimens were subjected to routine biochemical, microbiological, and histological evaluation. Tuberculous pleurisy was diagnosed if any of the following criteria was met: 1) positive results for a TB culture, acid-fast bacilli or TB polymerase chain reaction from the respiratory specimens; 2) histological analysis of the pleural tissue showing granulomatous inflammation with or without caseous necrosis or multinucleated giant cells; or 3) pleural effusion comprising lymphocyte-dominant exudates with adenosine deaminase concentration >40 U/L and a positive treatment response to 6 months of antituberculous therapy and if no alternative diagnosis for the effusion other than TB was appropriate, according to a previous study12. We used the definition of an immunocompromised condition as provided by Lee et al13.…”

A 30-year-old female Behçet’s disease patient with recurrent pleural and pericardial effusion and elevated adenosine deaminase levels: case report

“…In our case, the patient was assumed to have TB pericarditis and pleurisy due to lympho-dominant exudate with a high ADA level on effusion analysis. Although she had a negative result of IGRA, the negative predictive value of the test of peripheral blood is known to be relatively low in the diagnosis of TB pleurisy (17). Regarding the relationship between ADA and Behçet's disease, several studies have shown that plasma ADA levels are increased in patients with…”

Diagnostic utility of interferon-gamma release assay in extrapulmonary tuberculosis

“…Ariga et al (Ariga et al, 2007) reported that IGRAs showed a modest sensitivity of 78% and a specificity of 70% in the diagnosis of pleural TB, and Ates et al (Ates et al, 2011) reported a similar sensitivity of 70% and a lower specificity of 52%. Among 15 patients with pleurisy in our study, the IGRA showed a lower sensitivity of 38.5% and a specificity of 50.0%.…”