Novel biomarker analysis of pleural effusion enhances differentiation of tuberculous from malignant pleural effusion

Abstract

Lymphocytic pleurisy is commonly observed in tuberculosis and cancer. Noninvasive biomarkers are needed to distinguish tuberculous pleural effusion (TPE) from malignant pleural effusion (MPE) because current clinical diagnostic procedures are often invasive. We identified immune response biomarkers that can discriminate between TPE and MPE. Fourteen pleural effusion biomarkers were compared in 22 MPE patients and five TPE patients. Of the innate immunity biomarkers, the median levels of interleukin (IL)-1β and interferon-induced protein-10 (IP-10) were higher in TPE patients than in MPE patients (P<0.05 and P<0.01, respectively). Of the adaptive immunity biomarkers, the median levels of IL-13 and interferon-γ (IFN-γ) were higher in TPE patients than in MPE patients (P<0.05). In addition, the levels of basic fibroblast growth factor were higher in MPE patients than in TPE patients (P<0.05). Receiver operator characteristic analysis of these biomarkers was performed, resulting in the highest area under the curve (AUC) for IP-10 (AUC =0.95, 95% confidence interval, P<0.01), followed by IL-13 (AUC =0.86, 95% confidence interval, P<0.05). Our study shows that five biomarkers (IL-1β, IP-10, IFN-γ, IL-13, and basic fibroblast growth factor) have a potential diagnostic role in differentiating TPE from MPE, particularly in lung cancer-related MPE.

IL‐10 promotes malignant pleural effusion in mice by regulating TH1‐ and TH17‐cell differentiation and migration

“…Many studies have reported the level of CXCL10 to be higher in human MPE, which is in line with our result that CXCL10 was higher in human MPE than in corresponding blood (data not shown). Taken together, these findings indicated that CXCL10 may be involved in the immune response to pleural disease . Accordingly, we focused the experiments in this study on CXCL10.…”

The C-Type Lectin Receptor DC-SIGN Has an Anti-Inflammatory Role in Human M(IL-4) Macrophages in Response to Mycobacterium tuberculosis

“…Interestingly, IL-4 is one of the most detected cytokines in TB PE, and thus making probably the responsible signal to induce DC-SIGN expression in cells at this site ( 43 ). IL-13 is another cytokine that is present in the pleural cavity of active TB patients ( 44 ), and that is probably responsible for the mediating DC-SIGN expression in macrophages since its signaling pathway is considered to be equivalent to that of IL-4 ( 22 ). At the pulmonary tissue level, while we detected DC-SIGN-expressing cells with a morphology typical of dendritic cells and lymphocytes (likely B cells), there were also numerous DC-SIGN-expressing cells which also co-express the macrophage marker CD68 and CD163.…”

Application of Venn's diagram in the diagnosis of pleural tuberculosis using IFN-γ, IP-10 and adenosine deaminase

“…Even though the average performance of IP-10, in accordance with Dheda’s results, we presented a considerable number of false positives (5 malignancies, 1 endometriosis, 1 cardiac failure and 1 hepatic failure). In a study published in 2016, TB and malignant pleural effusions were compared using several biomarkers, including IFN-γ and IP-10 [ 34 ]. In their sample of 27 patients (5 pleural TB and 22 malignant pleural effusion), IP-10 presented the best AUC when compared to IFN-γ (AUC 0.950 and cut-off 4,005 pg/mL vs AUC 0.830 and 100.5 pg/mL), with both presenting the same sensitivity and specificity.…”