Interleukin -39 Expression in Pleural Effusion and Its Diagnostic Value for Tuberculous Pleurisy

Abstract

Objective: This study aimed to assess Interleukin-39 (IL-39) levels in various types of pleural effusion (PE), explore IL-39's diagnostic value in tuberculous pleurisy, analyze its correlation with other PE and tuberculosis indicators, and confirm the involvement of IL-39 in tuberculosis infection and the resulting inflammatory response.

Methods: This study enrolled 113 patients with PE caused by different etiologies: 20 with transudative effusion, 39 with malignant pleural effusion (MPE), 15 with uncomplicated parapneumonic effusion (UPPE), and 39 with tuberculous pleural effusion (TPE). Enzyme-linked immunosorbent assay (ELISA) was used to measure IL-39, interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α) levels in the pleural fluid (PF) of each group. Adenosine deaminase (ADA) activity was determined using the colorimetric method.

Results: IL-39 concentration was notably higher in the TPE compared to others. The IL-39 demonstrated an AUC of 0.944, with a cut-off value of 39.8 pg/mL, sensitivity of 94.9%, and specificity of 79.7% in distinguishing between the TPE and non-TPE. In discriminating between the TPE and MPE, the AUC for IL-39 was 0.941, with a cut-off value of 39.3 pg/mL, sensitivity of 94.9%, and specificity of 79.5%. For differentiating the TPE and UPPE, IL-39 yielded an AUC of 0.885, with a cut-off value of 235.0 pg/mL, sensitivity of 66.7%, and specificity of 100.0%. Moreover, based on these findings, multivariable diagnostic model and the rapid combination of IL-39 with other tuberculosis biomarkers (such as IFN-γ, TNF-α, and ADA) significantly enhanced the diagnostic and differential diagnostic performance for TPE. Additionally, IL-39, IFN-γ, TNF-α, and ADA levels in PF were positively correlated with each other.

Conclusion: IL-39 demonstrated good diagnostic and differential diagnostic value for TPE. Furthermore, the multivariate diagnostic model, as well as the joint detection of IL-39 with other tuberculosis biomarkers, can further increased the sensitivity or specificity. Additionally, IL-39 exhibited positive correlations with other tuberculosis biomarkers, suggesting its potential involvement in tuberculosis infection and the inflammatory response it may induce.

Keywords: Interleukin-39; diagnosis; pleural effusion; tuberculous pleurisy.

Figure 1

Flowchart of the study.

Figure 2

The level of PF parameters. (A) IL-39 levels across transudate, MPE, UPPE, and TPE. (B) Differences in IL-39 levels between TPE and non-TPE. (C) ADA levels across transudate, MPE, UPPE, TPE. (D) Differences in ADA levels between TPE and non-TPE. (E) IFN-γ levels across transudate, MPE, UPPE, TPE. (F) Differences in IFN-γ levels between TPE and non-TPE. (G) TNF-α levels across transudate, MPE, UPPE, TPE. (H) Differences in TNF-α levels between TPE and non-TPE. Horizontal bars denote the median. ns, not significant; *, P < 0.05; ***, P < 0.001; ****, P < 0.0001.

Figure 3

Diagnostic performance of multivariate model. (A) ROC curve comparison of Model 1 with IL-39, ADA, IFN-γ and TNF-α for distinguishing TPE from non-TPE. (B) Calibration plot of the multivariable Model 1.

Figure 4

ROC curve comparison of IL-39, ADA, IFN-γ and TNF-α for distinguishing TPE from MPE.

Figure 5

ROC curve comparison of IL-39, ADA, IFN-γ and TNF-α for distinguishing TPE from UPPE.

Figure 6

Correlation between IL-39 concentrations and PF related parameters in TPE, assessed via Spearman correlation coefficients. (A) Heatmap of the correlation between IL-39 and pleural fluid parameters in TPE. (B) Correlation analysis between IL-39 and total protein. (C) Correlation analysis between IL-39 and LDH. (D) Correlation analysis between IL-39 and glucose.

Figure 7

Spearman correlation coefficient analysis of four pleural markers. (A) Correlation analysis between IL-39 and IFN-γ. (B) Correlation analysis between IL-39 and TNF-α. (C) Correlation analysis between IL-39 and ADA. (D) Correlation analysis between IFN-γ and TNF-α. (E) Correlation analysis between ADA and IFN-γ. (F) Correlation analysis between ADA and TNF-α.