Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Clinical Center for Pleural Diseases, Capital Medical University, Beijing, China.
Microbiol Spectr. 2022 Aug 31;10(4):e0255321. doi: 10.1128/spectrum.02553-21. Epub 2022 Jul 26.
Accurate differential diagnosis is the key to choosing the correct treatment for pleural effusion. The present study aimed to assess whether interleukin 32 (IL-32) could be a new biomarker of tuberculous pleural effusion (TPE) and to explore the biological role of IL-32 in TPE. IL-32 levels were evaluated in the pleural effusions of 131 patients with undetermined pleural effusion from Wuhan and Beijing cohorts using an enzyme-linked immunosorbent assay method. Macrophages from TPE patients were transfected with IL-32-specific small interfering RNA (siRNA), and adenosine deaminase (ADA) expression was determined by real-time PCR and colorimetric methods. With a cutoff value of 247.9 ng/mL, the area under the curve of the receiver operating characteristic (ROC) curve for IL-32 was 0.933 for TPE, and the sensitivity and specificity were 88.4% and 93.4%, respectively. A multivariate logistic regression model with relatively good diagnostic performance was established. IL-32-specific siRNA downregulated ADA expression in macrophages, and IL-32γ treatment significantly induced ADA expression. Our results indicate that IL-32 in pleural effusion may be a novel biomarker for identifying patients with TPE. In addition, our multivariate model is acceptable to rule in or rule out TPE across diverse prevalence settings. Furthermore, IL-32 may modulate ADA expression in the tuberculosis microenvironment. (This study has been registered at ChiCTR under registration number ChiCTR2100051112 [https://www.chictr.org.cn/index.aspx].) Tuberculous pleural effusion (TPE) is a common form of extrapulmonary tuberculosis, with manifestations ranging from benign effusion with spontaneous absorption to effusion with pleural thickening, empyema, and even fibrosis, which can lead to a lasting impairment of lung function. Therefore, it is of great significance to find a rapid method to establish early diagnosis and apply antituberculosis therapy in the early stage. This study indicates that interleukin 32 (IL-32) in pleural effusion is a new high-potency marker to distinguish TPE from pleural effusions with other etiologies. A multivariate model combining age, adenosine deaminase (ADA), lactic dehydrogenase, and IL-32 may reliably rule in TPE in intermediate- or high-prevalence areas. Additionally, we observed that IL-32 might regulate ADA expression in macrophages in the tuberculosis microenvironment. Therefore, this study provides new insights into the role of IL-32 in the tuberculosis microenvironment.
准确的鉴别诊断是选择胸腔积液正确治疗方法的关键。本研究旨在评估白细胞介素 32 (IL-32) 是否可作为结核性胸腔积液 (TPE) 的新型生物标志物，并探讨 IL-32 在 TPE 中的生物学作用。采用酶联免疫吸附试验方法检测了来自武汉和北京队列的 131 例不明原因胸腔积液患者胸腔积液中的 IL-32 水平。用 IL-32 特异性小干扰 RNA (siRNA) 转染 TPE 患者的巨噬细胞，通过实时 PCR 和比色法测定腺苷脱氨酶 (ADA) 的表达。以 247.9ng/mL 为截断值，IL-32 的受试者工作特征 (ROC) 曲线下面积为 0.933，其敏感性和特异性分别为 88.4%和 93.4%。建立了具有较好诊断性能的多变量逻辑回归模型。IL-32 特异性 siRNA 下调巨噬细胞中 ADA 的表达，IL-32γ 处理可显著诱导 ADA 的表达。我们的研究结果表明胸腔积液中的 IL-32 可能是鉴别 TPE 患者的新型生物标志物。此外，我们的多变量模型可用于在不同流行率环境下纳入或排除 TPE。此外，IL-32 可能在结核微环境中调节 ADA 的表达。(本研究已在中国临床试验注册中心注册，注册号 ChiCTR2100051112[https://www.chictr.org.cn/index.aspx])。结核性胸腔积液 (TPE) 是一种常见的肺外结核形式，临床表现从良性积液自发吸收到胸腔积液增厚、积脓，甚至纤维化不等，这可能导致肺功能持续受损。因此，找到一种快速方法来建立早期诊断并在早期应用抗结核治疗具有重要意义。本研究表明，胸腔积液中的白细胞介素 32 (IL-32) 是区分 TPE 与其他病因胸腔积液的一种新型高效标志物。结合年龄、腺苷脱氨酶 (ADA)、乳酸脱氢酶和 IL-32 的多变量模型可能在中高流行地区可靠地诊断 TPE。此外，我们观察到 IL-32 可能调节结核微环境中巨噬细胞中的 ADA 表达。因此，本研究为 IL-32 在结核微环境中的作用提供了新的见解。
