Xuxiang Song,1,2,* Qipan Zhang,3,* Tiantian Cen,1,3,* Wei Fan,1,2 Weili Chen,1,2 Lun Guo,4 Yingying Du,1,2 Chengna Lv,2 Pan Tang,2 Zhaoxing Dong,5 Mingcai Li,6 Qunli Ding2 

1Health Science Center, Ningbo University, Ningbo, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Ningbo University, Ningbo, People’s Republic of China; 3Department of Infectious Diseases, The First Affiliated Hospital of Ningbo University, Ningbo, People’s Republic of China; 4Department of Respiratory Medicine, Suizhou Hospital, Hubei University of Medicine, Suizhou, Hubei, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, Ningbo Second Hospital, Ningbo, People’s Republic of China; 6School of Basic Medical Sciences and Zhejiang Key Laboratory of Pathophysiology, Health Science Center, Ningbo University, Ningbo, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Mingcai Li, Email limingcai@nbu.edu.cn Qunli Ding, Email dingqunli@nbu.edu.cn

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, pleural effusion, tuberculous pleurisy, diagnosis