Level of soluble programmed death ligand 1 in pleural effusion and peripheral blood of patients with tuberculous pleural effusion and its clinical implications

Objective To explore the level of soluble programmed death ligand 1 (sPD-L1) in pleural effusion and peripheral blood of patients with tuberculous pleural effusion (TPE) and elucidate its clinical implications. Methods Patients with newly diagnosed pleural effusion at the Second Affiliated Hospital of Soochow University from June 2012 to March 2013 were enrolled and divided into 3 groups of TPE, malignant pleural effusion (MPE) and non-tuberculous non-malignant pleural effusion (non-TPE non-MPE) according to the nature of pleural effusion. The level of sPD-L1 in pleural effusion and peripheral blood was analyzed by enzyme linked immunosorbent assay (ELISA) kit. Flow cytometry was used to detect the changes of immune cell subsets in pleural effusion. And the gene expressions of programmed death ligand 1 (PD-L1) and matrix metalloproteinase-3 (MMP-3) were detected in different effusions by reverse transcription-polymerase chain reaction (RT-PCR). Results A total of 77 newly diagnosed patients with pleural effusion were enrolled, 24 patients with TPE, 39 patients with MPE, 14 patients with non-TPE non-MPE. The level of sPD-L1 in TPE was higher than that in MPE and non-TPE non-MPE (4.2 (2.6-6.3), 1.4 (0.8-2.1), 1.8 (1.2-2.6) μg/L, P<0.001). No significant difference existed in the levels of sPD-L1 in peripheral blood samples (P=0.811). The average content of sPD-L1 in pleural effusion in all patients was statistically higher than that in peripheral blood (2.0 (1.4-3.7), 1.5 (1.0-2.0) μg/L, P=0.004). The proportion of CD8 subset, PD-L1 on CD14+ monocytes and the mRNA level of PD-L1, MMP-3 in TPE were higher than in MPE and non-TPE non-MPE (P=0.001, P<0.001, P<0.001), and the mRNA level of PD-L1 in TPE was positively correlated with the level of MMP-3 (r=0.887, P<0.001). Receiver operating characteristic (ROC) curve analysis showed that sPD-L1 had a sensitivity of 82.6%, a specificity of 83.8% and an area under curve (AUC) of 0.854 for differential diagnosis of TPE from other conditions. Combinations of sPD-L1, PD-L1 on CD14+ monocytes and adenosine deaminase (ADA) measurements further increased the sensitivity up to 91.3%, specificity up to 89.2% and AUC up to 0.989. Conclusion The elevated expression of sPD-L1 in tuberculous pleural effusion may aid the diagnosis of TPE. Key words: Pleural effusion; Tuberculosis; Programmed death ligand 1; Diagnosis