Conventional tests are not always helpful in making a diagnosis of tuberculous pleurisy. Many studies have investigated the usefulness of interferon (IFN)-gamma measurements in pleural fluid for the early diagnosis of tuberculous pleurisy. We conducted a metaanalysis to determine the accuracy of IFN-gamma measurements in the diagnosis of tuberculous pleurisy.
After a systematic review of English-language studies, sensitivity, specificity, and other measures of accuracy of IFN-gamma concentrations in the diagnosis of pleural effusion were pooled using random-effects models. Summary receiver operating characteristic curves were used to summarize overall test performance.
Twenty-two studies met our inclusion criteria. The summary estimates for IFN-gamma in the diagnosis of tuberculous pleurisy in the studies included were as follows: sensitivity, 0.89 (95% confidence interval [CI], 0.87 to 0.91); specificity, 0.97 (95% CI, 0.96 to 0.98); positive likelihood ratio, 23.45 (95% CI, 17.31 to 31.78); negative likelihood ratio, 0.11 (95% CI, 0.07 to 0.16); and diagnostic odds ratio, 272.7 (95% CI, 147.5 to 504.2).
IFN-gamma determination is a sensitive and specific test for the diagnosis of tuberculous pleurisy. The measurement of IFN-gamma levels in pleural effusions is thus likely to be a useful tool for diagnosing tuberculous pleurisy. The results of IFN-gamma assays should be interpreted in parallel with clinical findings and the results of conventional tests.
"In high burden settings such as South Africa, a high ADA level is frequently used to guide initiation of anti-TB therapy [4,5]. In this study, although ADA levels were 5 times higher in TB patients than in non-TB patients, using the laboratory accepted cut-point in Cape Town (30 U/L) roughly 20% of TB patients would have been missed and 1 in 10 incorrectly started on anti-TB therapy. "
[Show abstract][Hide abstract] ABSTRACT: The accuracy of currently available same-day diagnostic tools (smear microscopy and conventional nucleic acid amplification tests) for pleural tuberculosis (TB) is sub-optimal. Newer technologies may offer improved detection.
Smear-microscopy, adenosine deaminase (ADA), interferon gamma (IFN-gamma), and Xpert MTB/RIF [using an unprocessed (1 ml) and centrifuged (~20 ml) sample] test accuracy was evaluated in pleural fluid from 103 consecutive patients with suspected pleural TB. Culture for M.tuberculosis and/or histopathology (pleural biopsy) served as the reference standard. Patients were followed prospectively to determine their diagnostic categorisation.
Of 93 evaluable participants, 40 had definite-TB (reference positive), 5 probable-TB (not definite but treated for TB) and 48 non-TB (culture and histology negative, and not treated for TB). Xpert MTB/RIF sensitivity and specificity (95% CI) was 22.5% (12.4 - 37.6) and 98% (89.2 - 99.7), respectively, and centrifugation did not improve sensitivity (23.7%). The Xpert MTB/RIF internal positive control showed no evidence of inhibition. Biomarker specific sensitivity, specificity, PPV, and NPVs were: ADA (48.85 IU/L; rule-in cut-point) 55.3% (39.8 - 69.9), 95.2% (83.9 - 98.7), 91.4 (73.4 - 95.4), 69.7% (56.7 - 80.1); ADA (30 IU/L; clinically used cut-point) 79% (63.7 - 89), 92.7% (80.6 - 97.5), 91.0 (73.4 - 95.4), 82.7% (69.3 - 90.1); and IFN-gamma (107.7 pg/ml; rule-in cut-point) 92.5% (80.2 - 97.5), 95.9% (86.1 - 98.9), 94.9% (83.2 - 98.6), 93.9% (83.5 - 97.9), respectively (IFN-gamma sensitivity and NPV better than Xpert [p < 0.05] and rule-in ADA [p < 0.05]).
The usefulness of Xpert MTB/RIF to diagnose pleural TB is limited by its poor sensitivity. IFN-gamma is an excellent rule-in test and, compared to ADA, has significantly better sensitivity and rule-out value in a TB-endemic setting.
BMC Pulmonary Medicine 04/2014; 14(1):58. DOI:10.1186/1471-2466-14-58 · 2.40 Impact Factor
"However, in our study, in patients with TB, pleural IFN-γ concentration was only 2.4 times greater than the serum concentration. The sensitivity and specificity of IFN-γ measurements as a diagnostic marker of pleural TB ranged from 85.7 to 100%, and from 95 to 97%, respectively [12,26]. The methodology of IFN-γ determination used in most of the studies was similar and based on using commercial immunoenzymatic assays (ELISA). "
[Show abstract][Hide abstract] ABSTRACT: To evaluate and compare the diagnostic efficiency of serum (s) and pleural (p) levels of adenosine deaminase (ADA)-1, ADA-2, total ADA, and interferon-gamma (IFN-gamma) for the differential diagnosis of pleural tuberculosis (TB).
Clinical and analytic data of 93 consecutive patients with pleural effusions from May 2012 to February 2013 were prospectively evaluated. The study population included 43 pleural TB, 23 malignancies, and 27 other exudates. The median and interquartile range of ADA-1, ADA-2, total ADA, and IFN-gamma were evaluated according to their underlying diseases.
There were no significant differences in sADA-1 and sIFN-gamma values among each group. pADA-1, pADA-2, total pADA, and pIFN-gamma levels were significantly higher in patients with pleural TB than in other patients (p < 0.0001). As for pleural TB receiving operating characteristic (ROC) curves identified the following results. The best cut-off value for pADA-2 was 20.37 U/L and it yielded a sensitivity and specificity of 95.35% and 86%, respectively. Taking a cut-off value of 40.68 U/L for total pADA, the sensitivity and the specificity were found to be 88.37% and 88%, respectively. ROC curve identified 110 U/L as the best cut-off value for pIFN-gamma, while the sensitivity and the specificity were 74.42% and 68%, respectively. Finally, the best cut-off value for pADA-1 was 16.8 U/L and yielded a sensitivity and specificity of 69.77% and 68%, respectively.
To distinguish pleural TB, pleural levels of ADA-2 have the highest sensitivity among the different diagnostic parameters and may find a place as routine investigation for early detection of TB in the future.
Multidisciplinary respiratory medicine 03/2014; 9(1):12. DOI:10.1186/2049-6958-9-12 · 0.15 Impact Factor
"It has been well documented that TPE was enriched with CD4+CDw29+ T cells, which are thought to represent “memory” T cells, and these pleural CD4+CDw29+ cells, but not CD4+CDw29- cells, proliferated vigorously and produced high levels of IFN-γ when stimulated with purified protein derivative of MTB . High concentration of IFN-γ could always be found in TPE and served as a reasonable diagnostic biomarker for TPE . Our current data showed that exogenous IFN-γ notably enhanced ICAM-1 MFI of PMCs in vitro, while TPE didn’t increased ICAM-1 MFI. "
[Show abstract][Hide abstract] ABSTRACT: Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) have been demonstrated to be expressed on pleural mesothelial cells (PMCs), and to mediate leukocyte adhesion and migration; however, little is known about whether adhesion molecule-dependent mechanisms are involved in the regulation of CD4(+) T cells by PMCs in tuberculous pleural effusion (TPE).
Expressions of ICAM-1 and VCAM-1 on PMCs, as well as expressions of CD11a and CD29, the counter-receptors for ICAM-1 and VCAM-1, respectively, expressed on CD4(+) T cells in TPE were determined using flow cytometry. The immune regulations on adhesion, proliferation, activation, selective expansion of CD4(+) helper T cell subgroups exerted by PMCs via adhesion molecule-dependent mechanisms were explored.
Percentages of ICAM-1-positive and VCAM-1‒positive PMCs in TPE were increased compared with PMC line. Interferon-γ enhanced fluorescence intensity of ICAM-1, while IL-4 promoted VCAM-1 expression on PMCs. Percentages of CD11a(high)CD4(+) and CD29(high)CD4(+) T cells in TPE significantly increased as compared with peripheral blood. Prestimulation of PMCs with anti‒ICAM-1 or ‒VCAM-1 mAb significantly inhibited adhesion, activation, as well as effector regulatory T cell expansion induced by PMCs.
Our current data showed that adhesion molecule pathways on PMCs regulated adhesion and activation of CD4(+) T cells, and selectively promoted the expansion of effector regulatory T cells.
PLoS ONE 09/2013; 8(9):e74624. DOI:10.1371/journal.pone.0074624 · 3.23 Impact Factor
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