Monocytes subtypes from pleural effusion reveal biomarker candidates for the diagnosis of tuberculosis and malignancy

BACKGROUND: Pleural effusion is a common clinical condition caused by several respiratory diseases, including tuberculosis and malignancy. However, rapid and accurate diagnoses of tuberculous pleural effusion (TPE) and malignant pleural effusion (MPE) remain challenging. Although monocytes have been confirmed as an important immune cell in tuberculosis and malignancy, little is known about the role of monocytes subpopulations in the diagnosis of pleural effusion. METHODS: Pleural effusion samples and peripheral blood samples were collected from 40 TPE patients, 40 MPE patients, and 24 transudate pleural effusion patients, respectively. Chemokines (CCL2, CCL7, and CX3CL1) and cytokines (IL‐1β, IL‐17, IL‐27, and IFN‐γ) were measured by ELISA. The monocytes phenotypes were analyzed by flow cytometry. The chemokines receptors (CCR2 and CX3CR1) and cytokines above in different monocytes subsets were analyzed by real‐time PCR. Receiver operating characteristic curve analysis was performed for displaying differentiating power of intermediate and nonclassical subsets between tuberculous and malignant pleural effusions. RESULTS: CCL7 and CX3CL1 levels in TPE were significantly elevated in TPE compared with MPE and transudate pleural effusion. Cytokines, such as IL‐1β, IL‐17, IL‐27, and IFN‐γ, in TPE were much higher than in other pleural effusions. Moreover, CD14(+)CD16(++) nonclassical subset frequency in TPE was remarkably higher than that in MPE, while CD14(++)CD16(+) intermediate subset proportion in MPE was found elevated. Furthermore, CX3CL1‐CX3CR1 axis‐mediated infiltration of nonclassical monocytes in TPE was related to CX3CL1 and IFN‐γ expression in TPE. Higher expression of cytokines (IL‐1β, IL‐17, IL‐27, and IFN‐γ) were found in nonclassical monocytes compared with other subsets. Additionally, the proportions of intermediate and nonclassical monocytes in pleural effusion have the power in discriminating tuberculosis from malignant pleural effusion. CONCLUSIONS: CD14 and CD16 markers on monocytes could be potentially used as novel diagnostic markers for diagnosing TPE and MPE.