Interferon-Gamma Release Assay - Useful Tool for the Diagnosis of Pleural Tuberculosis

Background: Pleural tuberculosis represents a big problem to diagnose despite of many diagnostic tools. CD4+T-lymphocytes play an imprortant role in immune response against Mycobacterium tuberculosis. They are accumulated in pleural space affected with Mycobacterium tuberculosis and release an inflammatory cytokines (interferon-γ, interleukin-2). These cytokines interact with macrophages to stimulate effective antimycobacterial actions. The pleural fluid lymphocytes and interferon-γ level are elevated in many cases such as viral infections, malignancy or tuberculosis. We decided to evaluate a benefit of utilization of antigen specific Interferon-gamma release assay (IGRA) in pleural effusion (PE) to the diagnostics of pleural tuberculosis.

Methods: We present results of 29 patients with lymphocytic PE of unknown cause. The total leukocytes count, lymfocyte subsets by flow cytometry with monoclonal antibodies directed against the  T-lymphocyte antigens (CD3, CD4, CD8) and HLA DR antigen as a marker of T-lymphocyte activation were determined in PE. IGRA test was used to determine a level of specific interferon-gamma in PE and in whole blood too. Furthermore we analysed results of tuberculin skin test and Mycobacterium tuberculosis cultivation in the sputum and in PE.

Results: Of the 29 lymphocytic PE was IGRA test positive in 3 cases (10,3%). These patients had the pleural effusion with activated CD4+T-lymphocytes predominance, elevated CD4/CD8 ratio. Mycobacterium tuberculosis cultivation was negative in both sputum and pleural fluid except 1 patient with positive sputum culture. The tuberculin skin test was higher than 15 mm of all 3 patients. The clinical diagnosis of active pleural tuberculosis was confirmed in these patients. AntiTB treatment was successful of all them. Lymphocytic PE with negative IGRA test was in 26 patients (89,7%): malignancy in 7, heart failure effusion in 3, parapneumonic effusion in 8 and other pathological causes was in 8 patients.

Conclusions: Our results acknowledge that IGRA test applied to pleural fluid is very helpful to the diagnostics of pleural tuberculosis because the pleural fluid interferon-γ level is measured after stimulation of T-lymphocytes by tuberculous specific antigens. We conclude that another important benefit of interferon-γ release assays is the differential diagnostics of CD4+T-lymphocytic pleural effusions.